Hexahydrodibenzofuran derivatives

ABSTRACT

Disclosed are hexahydrodibenzofuran compounds of formula I, 
     
       
         
         
             
             
         
       
     
     the preparation thereof, the use thereof as components in liquid-crystalline media, and to electro-optical display elements which contain the liquid-crystalline media according to the invention.

The present invention relates to hexahydrodibenzofuran derivatives, tothe preparation thereof, to liquid-crystalline media comprising thesederivatives, and to electro-optical display elements containing theseliquid-crystalline media. In particular, the invention relates tohexahydrodibenzofuran derivatives of negative dielectric anisotropy.

Liquid crystals have found widespread use since the first commerciallyusable liquid-crystalline compounds were found about 30 years ago. Knownareas of application are, in particular, displays for watches and pocketcalculators, and large display panels as used in railway stations,airports and sports arenas. Further areas of application are displays ofportable computers and navigation systems and video applications. Forthe last-mentioned applications in particular, high demands are made ofthe response times and contrast of the images.

The spatial arrangement of the molecules in a liquid crystal has theeffect that many of its properties are direction-dependent. Ofparticular importance for use in liquid-crystal displays are theoptical, dielectric and elasto-mechanical anisotropies. Depending onwhether the molecules are oriented with their longitudinal axesperpendicular or parallel to the two plates of a capacitor, the latterhas a different capacitance; in other words, the dielectric constant εof the liquid-crystalline medium has different values for the twoorientations. Substances whose dielectric constant is larger when thelongitudinal axes of the molecules are oriented perpendicular to thecapacitor plates than when they are oriented parallel are referred to asdi-electrically positive. In other words, if the dielectric constantε_(∥) parallel to the longitudinal axes of the molecules is larger thanthe dielectric constant ε_(⊥) perpendicular to the longitudinal axes ofthe molecules, the dielectric anisotropy Δε=ε_(∥)−ε_(⊥) is greater thanzero. Most liquid crystals used in conventional displays fall into thisgroup.

Both the polarisability of the molecule and the permanent dipole momentplay a role for the dielectric anisotropy. On application of a voltageto the display, the longitudinal axis of the molecules orients itself insuch a way that the larger of the dielectric constants becomeseffective. The strength of the interaction with the electric fielddepends on the difference between the two constants. In the case ofsmall differences, higher switching voltages are necessary than in thecase of large differences. The introduction of suitable polar groups,such as, for example, nitrile groups or fluorine, into theliquid-crystal molecules enables a broad range of working voltages to beachieved.

In the case of the liquid-crystalline molecules used in conventionalliquid-crystal displays, the dipole moment oriented along thelongitudinal axis of the molecules is larger than the dipole momentoriented perpendicular to the longitudinal axis of the molecules. In themost widespread TN (“twisted nematic”) cells, a liquid-crystalline layerwith a thickness of only from about 5 to 10 μm is arranged between twoplane-parallel glass plates, onto each of which an electricallyconductive, transparent layer of tin oxide or indium tin oxide (ITO) hasbeen vapour-deposited as electrode. A likewise transparent alignmentlayer, usually consisting of a plastic (for example polyimides), islocated between these films and the liquid-crystalline layer. Thisalignment layer serves to bring the longitudinal axes of the adjacentliquid-crystalline molecules into a preferential direction throughsurface forces in such a way that, in the voltage-free state, they lieuniformly with the same orientation, flat or with the same small tiltangle, on the inside of the display surface. Two polarisation filmswhich only enable linear-polarised light to enter and escape are appliedto the outside of the display in a certain arrangement.

By means of liquid crystals in which the larger dipole moment isoriented parallel to the longitudinal axis of the molecule, veryhigh-performance displays have already been developed. In most caseshere, mixtures of from 5 to 20 components are used in order to achieve asufficiently broad temperature range of the mesophase and short responsetimes and low threshold voltages. However, difficulties are still causedby the strong viewing-angle dependence in liquid-crystal displays as areused, for example, for laptops. The best imaging quality can be achievedif the surface of the display is perpendicular to the viewing directionof the observer. If the display is tilted relative to the observationdirection, the imaging quality deteriorates drastically under certaincircumstances. For greater comfort, attempts are being made to maximisethe angle through which the display can be tilted from the viewingdirection of an observer without significantly reducing the imagingquality. Attempts have recently been made to improve the viewing-angledependence using liquid-crystalline compounds whose dipole momentperpendicular to the longitudinal axis of the molecule is larger thanthat parallel to the longitudinal axis of the molecule. The dielectricanisotropy Δε is negative. In the field-free state, these molecules areoriented with their longitudinal axis perpendicular to the glass surfaceof the display. Application of an electric field causes them to orientthemselves more or less parallel to the glass surfaces. In this way, ithas been possible to achieve an improvement in the viewing-angledependence. Displays of this type are known as VA-TFT (“verticallyaligned”) displays.

Development in the area of liquid-crystalline materials is still farfrom complete. In order to improve the properties of liquid-crystallinedisplay elements, attempts are constantly being made to develop novelcompounds which enable optimisation of such displays.

WO 02/055463 A1 discloses, inter alia, 3-monosubstituted and3,7-disubstituted 4,6-difluorodibenzofurans and -thiophenes, withoutgiving precise details of the physical or electro-optical properties.

It is therefore an object of the present invention to provide compoundshaving advantageous properties for use in liquid-crystalline media. Inparticular, they should have negative dielectric anisotropy, which makesthem particularly suitable for use in liquid-crystalline media for VAdisplays. Irrespective of the dielectric anisotropy corresponding to thedisplay type, compounds are desired which have a favourable combinationof the applicational parameters. Of these parameters, which are to beoptimised simultaneously, particular mention should be made of a highclearing point, a low rotational viscosity, an optical anisotropy in theuse range, and the properties which serve to achieve mixtures having thedesired liquid-crystalline phases over a broad temperature range.

This object is achieved in accordance with the invention by compounds ofthe general formula I

in whichm and n each, independently of one another, are 0, 1 or 2,

-   X¹, X² and X³ each, independently of one another, denote H, halogen,    CN or CF₃, preferably H, F, Cl, CN or CF₃,-   A¹ and A² each, independently of one another, denote 1,4-phenylene,    in which ═CH— may be replaced once or twice by ═N— and which may be    unsubstituted or mono- to tetrasubstituted, independently of one    another, by —CN, —F, —Cl, —Br, —I, unsubstituted or mono- or    polyfluorine- and/or -chlorine-substituted C₁-C₆-alkanyl,    unsubstituted or mono- or polyfluorine-and/or -chlorine-substituted    C₁-C₆-alkoxy, 1,4-cyclohexylene, 1,4-cyclohexenylene or    1,4-cyclohexadienylene, in which —CH₂— may be replaced once or    twice, independently of one another, by —O— or —S— in such a way    that heteroatoms are not linked directly, and which may be    unsubstituted or mono- or polysubstituted by —F and/or —Cl,    -   bicyclo[1.1.1]pentane-1,3-diyl, bicyclo[2.2.2]octane-1,4-diyl,        spiro[3.3]heptane-2,6-diyl, tetrahydropyran-2,5-diyl or        1,3-dioxane-2,5-diyl,-   Z¹ and Z² each, independently of one another, denote a single bond,    —CF₂O—, —OCF₂—, —CH₂CH₂—, —CF₂CF₂—, —CF₂CH₂—, —CH₂CF₂—, —CHF—CHF—,    —(CO)O—, —O(CO)—, —CH₂O—, —OCH₂—, —CF═CH—, —CH═CF—, —CF═CF—, —CH═CH—    or —C_C—;-   R¹ and R², independently of one another, denote hydrogen, an    alkanyl, alkoxy, alkenyl or alkynyl radical having 1 to 15 or 2 to    15 C atoms respectively which is unsubstituted, monosubstituted by    —CN or —CF₃ or mono- or polysubstituted by —F, —Cl, —Br and/or —I,    where one or more CH₂ groups in these radicals may also each,    independently of one another, be replaced by —O—, —S—, —SO₂—, —CO—,    —(CO)O—, —O(CO)— or —O(CO)O— in such a way that heteroatoms are not    linked directly, —F, —Cl, —Br, —I, —CN, —SCN, —NCS or —SF₅;    where-   A¹, A², Z¹, Z² may each have identical or different meanings if m or    n respectively is greater than 1, and    where    in the case where simultaneously n=0, m=0 and X¹, X² and X³ are not    equal to F, R¹ and R² then do not simultaneously denote H.

The compounds have predominantly negative Δε and are thereforeparticularly suitable for use in VA-TFT displays. The compoundsaccording to the invention preferably have a Δε of <-2 and particularlypreferably a Δε of <-4. They exhibit very good compatibility with theusual substances used in liquid-crystal mixtures for displays.

Furthermore, the compounds of the formula I according to the inventionhave values for the optical anisotropy Δn which are particularlysuitable for use in VA-TFT displays. The compounds according to theinvention preferably have a Δn of greater than 0.05 and less than 0.40.

The other physical, physicochemical or electro-optical parameters of thecompounds according to the invention are also advantageous for use ofthe compounds in liquid-crystalline media. The compounds orliquid-crystalline media comprising these compounds have, in particular,a sufficient breadth of the nematic phase and good low-temperature andlong-term stability as well as sufficiently high clearing points. Therotational viscosities of the compounds are advantageously low,particularly for m+n=0.

It is furthermore preferred for one or two of the radicals X¹, X² and X³to denote Cl or F, in particular fluorine. It is particularly preferredfor X² and X³ to denote H and X¹ not to denote hydrogen. Alternatively,X¹ is preferably H and at least one of the substituents X² and X³ is nothydrogen. X¹, X² and X³ are particularly preferably, independently ofone another, H or F. In a particularly preferred embodiment, X¹ istherefore fluorine and X² and X³ are hydrogen. Alternatively, it isparticularly preferred for X¹ to be H, X² to be F and X³ to be H or F.

In the case where the radical R¹ denotes a fluorine atom or fluorinatedalkyl, in particular if m simultaneously denotes 0, the formula I thenalso encompasses compounds which may have an overall positive dielectricanisotropy. Such compounds are then suitable for dielectrically positiveliquid-crystal mixtures which are used in displays, such as, forexample, of the TN-TFT or IPS (‘in-plane switching’) type. Therequirements of the other physical parameters, such as, for example, theviscosity, are substantially congruent over most applications. The saidcompounds are thus equally suitable for these purposes since they havefavourable values for the parameters, such as rotational viscosity, Δn,etc., and are suitable for the preparation of liquid-crystallinemixtures.

A¹ and A² are preferably and independently of one another an optionallysubstituted 1,4-phenylene, an optionally substituted 1,4-cyclohexylene,in which —CH₂— may be replaced once or twice by —O—, or an optionallysubstituted 1,4-cyclohexenylene. If n or m is 2, the rings A¹ and A² mayadopt identical or different meanings.

A¹ and A² are particularly preferably, independently of one another,

A¹ and A² are very particularly preferably 1,4-cyclohexylene ringsand/or optionally fluorine-substituted 1,4-phenylene rings.

Z¹ and Z² are preferably, independently of one another, a single bond,—CH₂O—, —OCH₂—, —CF₂O—, —OCF₂—, —CF₂CF₂—, —CH═CH—, —CF═CH—, —CH═CF— or—CF═CF—, particularly preferably, independently of one another, a singlebond, —CF₂O—, —OCF₂—, —CF₂CF₂—, —CH═CH—, —CF═CH—, —CH═CF—, —CH₂O—,—OCH₂— or —CF═CF—. Z¹ and Z² are very particularly preferably,independently of one another, a single bond, —CF₂O—, —OCF₂—, —CH₂O—,—OCH₂— or —CF═CF—, in particular a single bond.

If R¹ and R² in the formula I each, independently of one another,represent an alkanyl radical and/or an alkoxy radical (alkyloxy radical)having 1 to 15 C atoms, these are straight-chain or branched. Each ofthese radicals is preferably straight-chain, has 1, 2, 3, 4, 5, 6 or 7 Catoms and is accordingly preferably methyl, ethyl, propyl, butyl,pentyl, hexyl, heptyl, methoxy, ethoxy, propoxy, butoxy, pentoxy,hexyloxy or heptyloxy.

R¹ and R² in the formula I may each, independently of one another, alsobe an oxaalkyl radical, i.e. an alkanyl radical in which at least one ofthe non-terminal CH₂ groups has been replaced by —O—, preferablystraight-chain 2-oxapropyl (=methoxymethyl), 2- (=ethoxymethyl) or3-oxabutyl (=methoxyethyl), 2-, 3- or 4-oxapentyl, 2-, 3-, 4- or5-oxahexyl, or 2-, 3-, 4-, 5- or 6-oxaheptyl. In a corresponding manner,R¹ and R² in the formula I may also, independently of one another, bethioalkanyl or sulfonealkanyl radicals, i.e. alkanyl radicals in whichone CH₂ group has been replaced by —S— or —SO₂—.

R¹ and R² in the formula I may furthermore each, independently of oneanother, be an alkenyl radical having 2 to 15 C atoms which isstraight-chain or branched and has at least one C—C double bond. It ispreferably straight-chain and has 2 to 7 C atoms. Accordingly, it ispreferably vinyl, prop-1- or -2-enyl, but-1-, -2- or -3-enyl, pent-1-,-2-, -3- or -4-enyl, hex-1-, -2-, -3-, -4- or -5-enyl, or hept-1-, -2-,-3-, -4-, -5- or -6-enyl. If the two C atoms of the C—C double bond aresubstituted, the alkenyl radical can be in the form of the E and/or Zisomer (trans/cis). In general, the respective E isomers are preferred.

In the same way as for an alkanyl radical, at least one of the CH₂groups in an alkenyl radical may also have been replaced by oxygen,sulfur or —SO₂—. In the case of replacement by —O—, an alkenyloxyradical (having a terminal oxygen) or an oxaalkenyl radical (having anon-terminal oxygen) is then present.

R¹ and R² in the formula I may also, independently of one another, be analkynyl radical having 2 to 15 C atoms which is straight-chain orbranched and has at least one C—C triple bond.

R¹ and R² in the formula I may each, independently of one another, be analkanyl radical having 1 to 15 C atoms in which one CH₂ group has beenreplaced by —O— and one has been replaced by —CO—, where these arepreferably adjacent. This thus contains an acyloxy group —CO—O— or anoxycarbonyl group —O—CO—. This radical is preferably straight-chain andhas 2 to 6 C atoms. The following of these radicals are preferred here:acetoxy, propionyloxy, butyryloxy, pentanoyloxy, hexanoyloxy,acetoxymethyl, propionyloxymethyl, butyryloxymethyl, pentanoyloxymethyl,2-acetoxyethyl, 2-propionyloxyethyl, 2-butyryloxyethyl, 3-acetoxypropyl,3-propionyloxypropyl, 4-acetoxybutyl, methoxycarbonyl, ethoxycarbonyl,propoxycarbonyl, butoxycarbonyl, pentoxycarbonyl, methoxycarbonylmethyl,ethoxycarbonyl-methyl, propoxycarbonylmethyl, butoxycarbonylmethyl,2-(methoxycarbonyl)-ethyl, 2-(ethoxycarbonyl)ethyl,2-(propoxycarbonyl)ethyl, 3-(methoxy-carbonyl)propyl,3-(ethoxycarbonyl)propyl and 4-(methoxycarbonyl)butyl. Furthermore, analkanyl radical can also have an —O—CO—O— unit. Replacement of a CH₂group by only one —CO— group (carbonyl function) is also possible.

R¹ and R² in the formula I may each, independently of one another, be analkenyl radical having 2 to 15 C atoms in which a CH₂ group, preferablyin the vicinity of an unsubstituted or substituted —C═C— unit, has beenreplaced by —CO—, —CO—O—, —O—CO— or —O—CO—O—, where this radical may bestraight-chain or branched. The radical is preferably straight-chain andhas 4 to 13 C atoms. Particular preference is given here toacryloyloxymethyl, 2-acryloyloxyethyl, 3-acryloyloxypropyl,4-acryloyloxybutyl, 5-acryloyloxypentyl, 6-acryloyloxyhexyl,7-acryloyloxyheptyl, 8-acryloyloxyoctyl, 9acryloyloxynonyl,methacryloyloxymethyl, 2-methacryloyloxyethyl, 3-methacryloyloxypropyl,4-methacryloyloxybutyl, 5-methacryloyloxypentyl, 6-methacryloyloxyhexyl,7-methacryloyloxyheptyl and 8-methacryloyloxyoctyl. Correspondingly, aCH₂ group in the vicinity of a substituted —C≡C-unit in an alkynylradical may also be replaced by —CO—, —CO—O—, —O—CO— or —O—CO—O—.

R¹ and R² in the formula I may each, independently of one another, be analkanyl radical or alkoxy radical having 1 to 15 C atoms or an alkenylradical or alkynyl radical having 2 to 15 C atoms, each of which ismonosubstituted by —CN or —CF₃, where these are preferablystraight-chain. The substitution by —CN or —CF₃ is possible in anydesired position.

R¹ and R² in the formula I may each, independently of one another, be analkanyl radical in which two or more CH₂ groups have been replaced by—O— and/or —CO—O—, where this may be straight-chain or branched. It ispreferably branched and has 3 to 12 C atoms.

R¹ and R² in the formula I may each, independently of one another, be analkanyl radical or alkoxy radical having 1 to 15 C atoms or an alkenylradical or alkynyl radical having 2 to 15 C atoms, each of which ismono- or polysubstituted by F, Cl, Br and/or 1, where these radicals arepreferably straight-chain and halogen is preferably —F and/or —Cl. Inthe case of poly-substitution, halogen is preferably —F. The resultantradicals also include perfluorinated radicals, such as —CF₃. In the caseof monosubstitution, the fluorine or chlorine substituent can be in anydesired position, but is preferably in the ω-position.

R¹ and R² in the formula I may also each, independently of one another,be —F, —Cl, —Br, —I, —CN, —SCN, —NCS or —SF₅. In this case, thedielectric anisotropy increases towards more positive values. For veryparticularly strongly negative dielectric anisotropies, thesesubstituents should not be selected. However, they are preferred forhigh Δε.

R¹ and R² in the general formula I are particularly preferably,independently of one another, hydrogen or an alkanyl radical, alkoxyradical or alkenyl radical having 1 to 7 or 2 to 7 C atoms respectively,where each of these radicals is preferably unsubstituted ormonosubstituted or polysubstituted by halogen.

R¹ and R² are very particularly preferably, independently of oneanother, hydrogen or an alkanyl radical, alkoxy radical or alkenylradical having 1 to 7 or 2 to 7 C atoms respectively, where each ofthese radicals is preferably unsubstituted.

In the case where m=0, R¹ preferably denotes an alkyl or alkoxy group, Hor F, particularly preferably an alkoxy group having 1-6 C atoms.

For the said substituents R¹ and R², the restriction mentioned at theoutset applies in the case where m and n are 0 and X¹, X² and X³ are notequal to F. Furthermore, particularly in the case where m and n are 0,R¹ and R² preferably do not simultaneously denote H.

In connection with the present invention, halogen denotes fluorine,chlorine, bromine or iodine, in particular fluorine or chlorine.

In connection with the present invention, the term “alkyl”—unlessdefined otherwise elsewhere in this description or in the claims—denotesa straightchain or branched aliphatic hydrocarbon radical having 1 to 15(i.e. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15) carbon atoms.This radical is unsubstituted or monosubstituted or polysubstituted byfluorine, chlorine, bromine, iodine, carboxyl, nitro, —NH₂, —N(alkanyl)₂and/or cyano, where the polysubstitution can take place with identicalor different substituents. If this alkyl radical is a saturated radical,it is also referred to as “alkanyl”. Furthermore, the term “alkyl” alsoencompasses hydrocarbon radicals which are unsubstituted orcorrespondingly mono- or polysubstituted by identical or differentsubstituents, in particular by —F, —Cl, —Br, —I and/or —CN or —CF₃, andin which one or more CH₂ groups may be replaced by —O— (“alkoxy”,“oxaalkyl”), —S— (“thioalkyl”), —SO₂—, —CH═CH— (“alkenyl”), —C≡C—(“alkynyl”), —CO—O—, —O—CO— or —O—CO—O— in such a way that hetero atoms(O or S) in the chain are not linked directly to one another.

Preferred compounds of the general formula I have a total of zero, one,two or three units -Z¹-A¹-and/or -Z²-A²-, i.e. m+n=0, 1, 2 or 3 where mand n are each 0, 1, 2 or 3. If two or three units -Z¹-A¹- and/or—Z²-A²- are present, they may be bonded to only one side of the molecule(i.e. m=2 or 3 and n=0 or n=2 or 3 and m=0) or also to both sides of themolecule. Preferably, m or n is 0. Particularly preferably, m+n=0, 1 or2 and very particularly 0 or 1.

Preferred compounds of the formula I for which m+n=0 are represented bythe following formula:

in which

R¹, R¹, X¹, X² and X³ have the same and the same preferred meanings asdefined above for the formula I.

In the case where R¹ is hydrogen, at least one group from X¹, X² and X³is preferably a fluorine substituent, in particular X¹.

Preferred compounds of the formula I for which m+n=1 are represented bythe following formulae:

in which

R¹, R², A¹, A², X¹, X², X³, Z² and Z² have the same and the samepreferred meanings as defined above for the formula I.

Preferred compounds of the formula I for which m+n=2 are represented bythe following formulae:

in which

-   -   R¹, R², A¹, A², X¹, X², X³, Z¹ and Z² have the same and the same        preferred meanings as defined above for the formula I.

If A¹, A², Z¹ or Z² occurs twice in the formulae Ie and If, it may ineach case have identical or different meanings.

Preferred compounds of the formula I for which m+n=3 are represented bythe following formulae:

in which

R¹, R², A¹, A², X¹, X², X³, Z¹, Z² and Y have the same and the samepreferred meanings as defined above for the formula I.

If A¹, A², Z¹ or Z² occurs more than once in the formulae Ig to Ij, itmay in each case have identical or different meanings.

Particular preference is given to compounds of the formulae Ia, Ib, Ic,Id, Ie and If, in particular of the formulae Ia, Ib and Ic, according tothe invention.

Very particularly preferred compounds of the formula Ia are thefollowing:

in which

R¹¹ and R²² denote an alkyl radical having up to 8 C atoms.

In the case where R¹¹ is bonded directly to the ring, R¹¹ may preferablyalso denote F, as in the compounds of the following formulae:

Of the compounds of the formulae Ia-1 to Ia-12, further preference isgiven to those of the formulae Ia-1 to Ia-4, in particular compounds ofthe formulae Ia-1 and Ia-3.

Of the preferred compounds of the formula Ib according to the invention,particular preference is given to the following:

in whichp in each case, independently of one another, is 0 to 4, preferably 0, 1or 2, and

R¹¹ and R²² have the same meanings as defined above.

Of the compounds 1b, particular preference is given to those containinga cyclohexyl ring.

Above and below, the moiety

in the sub-formulae preferably denotes a moiety of the formula

If p in the formulae occurs more than once, it may in each case haveidentical or different meanings.

Of the preferred compounds of the formula Ic according to the invention,particular preference is given to the following:

in which

R¹¹, R²² and p have the same meanings as defined above. Of the compoundsof the formulae Ic1-Ic24, compounds of the formulae containing anunsubstituted or substituted 1,4-phenylene ring and the compound 1c-13are most preferred.

Of the preferred compounds of the formula Id according to the invention,particular preference is given to the following:

in which

R¹¹, R²² and p have the same meanings as defined above. If p in theformulae occurs more than once, it may in each case have identical ordifferent meanings.

Of the compounds of the formulae Id-1 to Id-84, preference is given tocompounds of the formulae in which the parent structure is substitutedon the left by an aryl radical and/or the parent structure is linked onthe right to a cyclohexyl radical, i.e. the compounds of the formulaeId-1 to Id-18, Id-31 to Id-54 and Id-67 to Id-72. Overall, particularpreference is given to the compounds of the formulae Id-1 to Id-13 andId-67 to Id-72, furthermore Id-13 to Id-18, Id-31 to Id-38 and Id-73 toId-84; very particularly the formulae Id-1, Id-2, Id-3, Id-4, Id-67 andId-68.

Of the preferred compounds of the formula Ie according to the invention,particular preference is given to the following:

in which

R¹¹, R²² and p have the same meanings as defined above.

If p in the formulae occurs more than once, it may in each case haveidentical or different meanings.

Of the compounds of the formulae Ie-1 to le-42, compounds of theformulae containing an unsubstituted or substituted 1,4-phenylene ringare most preferred.

Of the preferred compounds of the formula If according to the invention,particular preference is given to the following:

in which

R¹¹, R²² and p have the same meanings as defined above. If p in theformulae occurs more than once, it may in each case have identical ordifferent meanings.

Of the compounds of the formulae If-1 to If-82, the compounds of theformulae containing at least one 1,4-cyclohexylene ring are mostpreferred, in particular containing two cyclohexylene rings (If-61 toIf-71) or containing one cyclohexylene ring directly on the parentstructure (If-26 to If-49). Particular preference is given to compoundsof the formula If-61.

In the sub-formulae of the formulae Ia to Ih, the moiety

preferably denotes a moiety of the formula

If radicals or substituents of the compounds according to the inventionor the compounds according to the invention themselves are in the formof optically active or stereoisomeric radicals, substituents orcompounds since they have, for example, a centre of asymmetry, these arelikewise encompassed by the present invention. It goes without sayinghere that the compounds of the general formula I according to theinvention may exist in isomerically pure form, for example as pureenantiomers, diastereomers, E or Z isomers, trans or cis isomers, or asa mixture of a plurality of isomers in any desired ratio, for example asa racemate, E/Z isomer mixture or as a cis/trans isomer mixture.

The 1,4-substituted cyclohexyl ring of the formula

in the compounds according to the invention and in the other componentsof liquid-crystalline media preferably has the trans configuration, i.e.the two substituents are both in the equatorial position in thethermodynamically preferred chair conformation.

Synthesis of the Compounds:

The compounds of the general formula I can be prepared by methods knownper se, as described in the literature (for example in the standardworks, such as Houben-Weyl, Methoden der organischen Chemie [Methods ofOrganic Chemistry], Georg-Thieme-Verlag, Stuttgart), to be precise underreaction conditions which are known and suitable for the said reactions.Use can be made here of variants known per se which are not mentionedhere in greater detail.

If desired, the starting materials can also be formed in situ by notisolating them from the reaction mixture, but instead immediatelyconverting them further into the compounds of the general formula I.

The syntheses of various compounds of the general formula I according tothe invention are described by way of example in the examples. Thestarting substances can be obtained by generally accessible literatureprocedures or are commercially available. The reaction types describedare to be regarded as known from the literature.

The compounds of the formula I encompass all eight stereoisomers whichemanate from the possible configurations of the hexahydrobenzofuran ringwith respect to positions 3, 4a and 9b of the ring system of the generalformula:

Particular preference is given to the stereoisomers in which a translink of the O-heterocyclic ring system to the cyclohexane ring ispresent and at the same time the substituent on C-3 is arranged in thetrans configuration to the substituent on C-9b (the furan ring here isregarded as a substituent of the cyclohexane ring). This applies to theparticularly preferred stereoisomers having the relative (3R*, 4aR*,9bS*)-configuration. The asterisk stands for the relative configuration,which has the same meaning as the two mirror-image, absoluteconfigurations.

Due to this stereochemistry, the ring system takes on a flat geometryand the entire molecule takes on a more stretched shape.

A part-aspect of the invention relates to processes for the preparationof the compounds of the formula I according to the invention. Theprocesses are subject to a common synthesis strategy, which is explainedbelow.

A preferred process for the preparation of compounds of type 1, whichare analogous to compounds of the formula I, is depicted in Scheme 1.The synthesis can be matched to the compounds of the formula 1 desiredin each case through the choice of suitable starting materials 3 and 4.These starting materials are either commercially available or they canbe synthesised following processes which have already been published.

The organolithium derivative of compound 3 adds onto the cyclohexylketone 4. The resultant alcohol readily dehydrates on treatment withp-TsOH to give the cyclohexene 5 analogously to P. Kirsch et al., Angew.Chem. Int. Ed. (1998), 37, 484-489. Hydroboration oxidation of thedouble bond using BH₃/THF complex gives the secondary alcohol 6. Thealkoxide of compound 6 cyclises under the reaction conditions indicatedto give the target compound 1. Conventional laboratory separation andpurification methods give the particularly preferred (3R*, 4aR*,9bS*)-configured stereoisomers of the compounds of the formula 1.

Preference is likewise given to synthetic processes via the ketointermediate II, since compound 11 can be functionalised in differentways below. The synthesis of the ketone 11 is likewise carried out viathe reaction sequence depicted in Scheme 1 using 1,4-cyclohexanedionemonoethylene ketal 7 as starting material (cf. Scheme 2). After thering-closure reaction to give 10, the ketal protecting group is cleavedoff in acidic medium (cf. Kirsch et al.).

The further functionalisation of 11 can then be carried out in variousways (cf. Scheme 3 and Scheme 4).

The reaction of 11 with a suitable Grignard reagent (cf. Scheme 3) or anorganolithium compound and dehydration of the resultant alcohol andfinal catalytic hydrogenation gives the target compound 12. Thepreferred (3R*,4aR*, 9bS-configured stereoisomers of compound 12 areobtained via conventional laboratory separation methods.

Wittig olefin formation reactions are furthermore suitable forderivatisation (cf. Scheme 4). After reaction with Wittig reagents andsubsequent hydrogenation of the double bond formed, a separable isomermixture of the target compound 13 is again formed.

Particular preference is also given to functionalisations via theintermediate 14, which is accessible in diastereoisomerically pure formin three steps from 11 (cf. Scheme 5).

The chain lengthening starting from 14 can then in turn be initiated viathe addition of a Grignard compound or by olefin formation using aWittig reagent (cf. Scheme 6).

The reaction schemes depicted should only be regarded as illustrative.The person skilled in the art will be able to carry out correspondingvariations of the syntheses presented and also follow other suitablesynthetic routes in order to obtain compounds of the formula I. Thus,for example, the compound of the formula 7 can have a different acetalprotecting group of the formula >C(O-alkyl)₂ or >C(cyclo-OCH₂CH₂CH₂O).

A common aspect of the processes for the preparation of compounds of theformula I is therefore that they include a process step in which afluorobenzene compound is condensed in the ortho position with acyclohexanone compound. Specifically, this is a fluorobenzene compoundof the formula 3 (Schemes 1 and 2) or a cyclohexanone compound of theformula 4 or 7 in accordance with their definition generalised as above.For the process, precursors of I may likewise be the subject of theprocess steps described and are only derivatised on the variablesubstituents of the rings at a later time. The process is furthermoredistinguished by the fact that it includes a process step in which a1-(2-halophenyl)cyclohexene compound is hydroborated on the double bondof the cyclohexene. These compounds are preferably compounds of theformula 5 or 8, where the acetal group in 8 can be varied as for formula7. The process furthermore includes a process step in which the2-(2-halophenyl)cyclohexanol compound formed is cyclised to give atetrahydrodibenzofuran derivative.

The cyclisation is carried out under the action of a base, preferably bymeans of a strong base, such as, for example, sodium hydride orpotassium hydride. The reaction is carried out at between 20 and 140°C., depending on the solvent and reaction rate.

Further details on the process are revealed in the examples, theparameters of which are representative of the process according to theinvention. The person skilled in the art will be able to generaliseindividual reaction conditions or adapt them to the individual case.

The starting materials are preferably 2-fluorobenzene derivatives,particularly preferably 2,3-difluoro derivatives. The direct processproduct is optionally further derivatised to give the desiredliquid-crystalline or mesogenic compounds.

As already mentioned, the compounds of the general formula I can be usedin liquid-crystalline media.

The present invention therefore also relates to a liquid-crystallinemedium comprising at least two liquid-crystalline compounds, comprisingat least one compound of the general formula I.

The present invention also relates to liquid-crystalline mediacomprising 2 to 40, preferably 4 to 30, components as furtherconstituents besides one or more compounds of the formula I according tothe invention. These media particularly preferably comprise 7 to 25components besides one or more compounds according to the invention.These further constituents are preferably selected from nematic ornematogenic (monotropic or isotropic) substances, in particularsubstances from the classes of the azoxybenzenes, benzylideneanilines,biphenyls, terphenyls, 1,3-dioxanes, 2,5-tetrahydropyrans, phenyl orcyclohexyl benzoates, phenyl or cyclohexyl esters ofcyclohexanecarboxylic acid, phenyl or cyclohexyl esters ofcyclohexylbenzoic acid, phenyl or cyclohexyl esters ofcyclohexylcyclohexane-carboxylic acid, cyclohexylphenyl esters ofbenzoic acid, of cyclohexane-carboxylic acid or ofcyclohexylcyclohexanecarboxylic acid, phenylcyclo-hexanes,cyclohexylbiphenyls, phenylcyclohexylcyclohexanes,cyclohexyl-cyclohexanes, cyclohexylcyclohexylcyclohexenes,1,4-biscyclohexyl-benzenes, 4′,4′-biscyclohexylbiphenyls, phenyl- orcyclohexylpyrimidines, phenyl- or cyclohexylpyridines, phenyl- orcyclohexyldioxanes, phenyl- or cyclohexyl-1,3-dithianes,1,2-diphenylethanes, 1,2-dicyclohexylethanes,1-phenyl-2-cyclohexylethanes,1-cyclohexyl-2-(4-phenylcyclohexyl)ethanes,1-cyclohexyl-2-biphenylethanes, 1-phenyl-2-cyclohexylphenylethanes,optionally halogenated stilbenes, benzyl phenyl ethers, tolans andsubstituted cinnamic acids. The 1,4-phenylene groups in these compoundsmay also be mono- or polyfluorinated.

The most important compounds suitable as further constituents of mediaaccording to the invention can be characterised by the formulae (II),(III), (IV), (V) and (VI):

R′-L-E-R″  (II)

R′-L-COO-E-R″  (III)

R′-L-COO-E-R″  (IV)

R′-L-CH₂CH₂-E-R″  (V)

R′-L-CF₂O-E-R″  (VI)

In the formulae (II), (III), (IV), (V) and (VI), L and E, which may beidentical or different, each, independently of one another, denote adivalent radical from the group formed by -Phe-, -Cyc-, -Phe-Phe-,-Phe-Cyc-, -Cyc-Cyc-, -Pyr-, -Dio-, -Thp-, -G-Phe- and -G-Cyc- and theirmirror images, where Phe denotes unsubstituted or fluorine-substituted1,4-phenylene, Cyc denotes trans-1,4-cyclohexylene or1,4-cyclohexenylene, Pyr denotes pyrimidine-2,5-diyl orpyridine-2,5-diyl, Dio denotes 1,3-dioxane-2,5-diyl, Thp denotestetrahydropyran-2,5-diyl and G denotes 2-(trans-1,4-cyclohexyl)ethyl,pyrimidine-2,5-diyl, pyridine-2,5-diyl, 1,3-dioxane-2,5-diyl ortetrahydropyran-2,5-diyl.

One of the radicals L and E is preferably Cyc or Phe. E is preferablyCyc, Phe or Phe-Cyc. The media according to the invention preferablycomprise one or more components selected from the compounds of theformulae (II), (III), (IV), (V) and (VI) in which L and E are selectedfrom the group consisting of Cyc and Phe and simultaneously one or morecomponents selected from the compounds of the formulae (II), (III),(IV), (V) and (VI) in which one of the radicals L and E is selected fromthe group consisting of Cyc and Phe and the other radical is selectedfrom the group consisting of -Phe-Phe-, -Phe-Cyc-, -Cyc-Cyc-, -G-Phe-and -G-Cyc-, and optionally one or more components selected from thecompounds of the formulae (II), (III), (IV), (V) and (VI) in which theradicals L and E are selected from the group consisting of -Phe-Cyc-,-Cyc-Cyc-, -G-Phe- and -G-Cyc-.

In a smaller sub-group of the compounds of the formulae (II), (III),(IV), (V) and (VI), R′ and R″ each, independently of one another, denotealkyl, alkenyl, alkoxy, alkoxyalkyl (oxaalkyl), alkenyloxy oralkanoyloxy having up to 8 C atoms. This smaller sub-group is calledgroup A below, and the compounds are referred to by the sub-formulae(IIa), (IIIa), (IVa), (Va) and (VIa). In most of these compounds, R′ andR″ are different from one another, one of these radicals usually beingalkyl, alkenyl, alkoxy or alkoxyalkyl (oxaalkyl).

In another smaller sub-group of the compounds of the formulae (II),(III), (IV), (V) and (VI), which is known as group B, E denotes

In the compounds of group B, which are referred to by the sub-formulae(IIb), (IIIb), (IVb), (Vb) and (VIb), R′ and R″ are as defined for thecompounds of the sub-formulae (IIa) to (VIa) and are preferably alkyl,alkenyl, alkoxy or alkoxyalkyl (oxaalkyl).

In a further smaller sub-group of the compounds of the formulae (II),(III), (IV), (V) and (VI), R″ denotes —CN. This sub-group is referred tobelow as group C, and the compounds of this sub-group arecorrespondingly described by sub-formulae (IIc), (IIIc), (IVc), (Vc) and(VIc). In the compounds of the sub-formulae (IIc), (IIIc), (IVc), (Vc)and (VIc), R′ is as defined for the compounds of the sub-formulae (IIa)to (VIa) and is preferably alkyl, alkenyl, alkoxy or alkoxyalkyl(oxaalkyl).

Besides the preferred compounds of groups A, B and C, other compounds ofthe formulae (II), (III), (IV), (V) and (VI) having other variants ofthe proposed substituents are also customary. All these substances areobtainable by methods which are known from the literature or analogouslythereto.

Besides the compounds of the general formula I according to theinvention, the media according to the invention preferably comprise oneor more compounds from groups A, B and/or C. The proportions by weightof the compounds from these groups in the media according to theinvention are:

group A:from 0 to 90%, preferably from 20 to 90%, in particular from 30 to 90%.group B:from 0 to 80%, preferably from 10 to 80%, in particular from 10 to 70%.group C:from 0 to 80%, preferably from 5 to 80%, in particular from 5 to 50%.

The media according to the invention preferably comprise from 1 to 40%,particularly preferably from 5 to 30%, of the compounds of the formula Iaccording to the invention. Preference is furthermore given to mediacomprising more than 40%, in particular from 45 to 90%, of compounds ofthe formula I according to the invention. The media preferably compriseone, two, three, four or five compounds of the formula I according tothe invention.

Examples of the compounds of the formulae (II), (III), (IV), (V) and(VI) are the compounds shown below:

where R^(a) and R^(b) independently of one another, denote—C_(p)H_(2p+1) or —OC_(p)H_(2p+1), and p=1, 2, 3, 4, 5, 6, 7 or 8, andL¹ and L², independently of one another, denote —H or —F,

where m and n, independently of one another, denote 1, 2, 3, 4, 5, 6, 7or 8.

The media according to the invention are prepared in a mannerconventional per se. In general, the components are dissolved in oneanother, preferably at elevated temperature. By means of suitableadditives, the liquid-crystalline phases of the present invention can bemodified in such a way that they can be used in all types ofliquid-crystal display element that have been disclosed hitherto.Additives of this type are known to the person skilled in the art andare described in detail in the literature (H. Kelker/ R. Hatz, Handbookof Liquid Crystals, Verlag Chemie, Weinheim, 1980). For example,pleochroic dyes can be used for the production of coloured guest-hostsystems or substances can be added in order to modify the dielectricanisotropy, the viscosity and/or the alignment of the nematic phases.

Owing to their negative Δε, the compounds of the formula I areparticularly suitable for use in VA-TFT displays.

The present invention therefore also relates to electro-opticalliquid-crystal display elements containing a liquid-crystalline mediumaccording to the invention.

The invention is explained in greater detail below with reference toworking examples, but without intending to be restricted thereby.

Besides the usual and well-known abbreviations, the followingabbreviations are used:

C: crystalline phase; N: nematic phase; Sm: smectic phase; I: isotropicphase. The numbers between these symbols show the transitiontemperatures of the substance concerned.

Temperature data are in ° C., unless indicated otherwise.

Physical, physicochemical or electro-optical parameters are determinedby generally known methods, as described, inter alia, in the brochure“Merck Liquid Crystals—Licristal®—Physical Properties of LiquidCrystals—Description of the Measurement Methods”, 1998, Merck KGaA,Darmstadt.

Above and below, Δn denotes the optical anisotropy (589 nm, 20° C.) andΔε denotes the dielectric anisotropy (1 kHz, 20° C.). The dielectricanisotropy Δε is determined at 20° C. and 1 kHz. The optical anisotropyΔn is determined at 20° C. and a wavelength of 589.3 nm.

The Δε and Δn values, the clearing point (cl.p.) and the rotationalviscosity (γ₁) of the compounds according to the invention are obtainedby linear extrapolation from liquid-crystalline mixtures consisting of 5to 10% of the respective compound according to the invention and 90-95%of the commercially available liquid-crystal mixture ZLI-2857 (for Δε)or ZLI-4792 (for Δn, cl.p., γ₁) (mixtures, Merck KGaA, Darmstadt).

The abbreviations have the following meanings:

MTBE methyl t-butyl ether THF tetrahydrofuran DMF dimethylformamide

i. vac. in vacuo (about 10⁻² bar)sat. saturatedn-BuLi n-butyllithium, solution in hexane

EXAMPLES

The starting substances can be obtained in accordance with generallyaccessible literature procedures or are commercially available. Thereactions described are known from the literature.

1. (±)-(3R*, 4aR*,9bS*)-7-ethoxy-6-fluoro-3-propyl-1,2,3,4,4a,9b-hexahydrodibenzofuran 1.18-(4-Ethoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]decan-7-ol

270.2 g (1.70 mol) of 2,3-difluoroethoxybenzene are initially introducedin 1200 ml of THF, and 1100 ml (1.75 mol) of n-BuLi (15% soln. inhexane) are added at −70° C. After 1 h at this temperature, a solutionof 270.2 g (1.70 mol) of 1,4-cyclohexanedione monoethylene ketal in 800ml of THF is metered in, and the batch is stirred for 1 h. The reactionmixture is warmed to 0° C. and hydrolysed using 4 N HCl. The solution isextracted with MTBE, and the combined organic phases are washed withsat. sodium chloride solution and dried using sodium sulfate. The crudeproduct remaining after removal of the solvents under reduced pressure(609.8 g of red-brown oil) is used directly for the next reaction.

1.2 8-(4-Ethoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]dec-7-ene

609 g (about 1.94 mol) of crude8-(4-ethoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]decan-7-ol in 2000 mlof toluene are heated on a water separator for 2 h together with 220 ml(3.93 mol) of ethylene glycol with addition of 36.1 g (0.19 mol) ofp-toluenesulfonic acid monohydrate. After cooling, the batch is washedsuccessively with water, sat. sodium hydrogencarbonate solution and sat.sodium chloride solution. The solution is dried using sodium sulfate andconcentrated to dryness. The crude product (507 g of orange oil) iscrystallised from ethanol at −20° C., giving8-(4-ethoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]dec-7-ene as yellowsolid.

1.3 8-(4-Ethoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]decan-7-ol

1400 ml (1.40 mol) of borane/THF complex (1 M solution) are added at −7°C. to a solution of 320.0 g (1.08 mol) of8-(4-ethoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]dec-7-ene in 3000 mlof THF, and the reaction mixture is stirred at room temperature for 3 h.262 ml (4.50 mol) of ethanol, 650 ml (2.6 mol) of aqueous sodiumhydroxide solution (4 M) and 360 ml (4.11 mol) of aqueous hydrogenperoxide soln. (35%) are added successively to the batch, during whichthe internal temperature does not exceed 47° C. (ice bath). When theaddition is complete, the mixture is refluxed for 2 h, and the solutionis cooled, added to water and stirred vigorously. The organic phase isseparated off, and the aqueous phase is extracted with MTBE. Thecombined organic phases are washed with sat. sodium chloride solutionand dried using sodium sulfate. The solution is concentrated to dryness,and the crude product (336 g of yellow oil) is purified by columnchromatography (SiO₂, dichloromethane: MTBE=8:2), giving8-(4-ethoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]decan-7-ol aspale-yellow oil.

1.4 (±)-(4aR*,9bS*)-7-Ethoxy-6-fluoro-1,4,4a,9b-tetrahydro-2H-spiro-[dibenzo[b,d]furan-3,2′-1,3-dioxolane]

50.0 g (1.25 mol) of sodium hydride (60% suspension in mineral oil) arewashed repeatedly with n-pentane and suspended in 3000 ml of toluene.The suspension is heated to 90° C., and a solution of 145.0 g (0.46 mol)of 8-(4-ethoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]decan-7-ol in 700ml of DMF is slowly metered in. The batch is stirred at 90° C. for 30 h,cooled and hydrolysed using water. The mixture is neutralised byaddition of 2 N hydrochloric acid, and the organic phase is separatedoff. The aqueous phase is extracted with toluene, and the combinedorganic phases are washed with sat. sodium chloride solution. Thesolution is dried using sodium sulfate and concentrated to dryness underreduced pressure. The crude product obtained is recrystallised fromethanol at 5° C., giving (±)-(4aR*,9bS*)-7-ethoxy-6-fluoro-1,4,4a,9b-tetrahydro-2H-spiro-[dibenzo[b,d]-furan-3,2′-1,3-dioxolane]as colourless solid.

1.5 (±)-(4aR*,9bS*)-7-Ethoxy-6-fluoro-1,4,4a,9b-tetrahydro-2H-dibenzofuran-3-one

135.0 g (459 mmol) of (±)-(4aR*,9bS*)-7-ethoxy-6-fluoro-1,4,4a,9b-tetrahydro-2H-spiro[dibenzo[b,d]furan-3,2′-1,3-dioxolane]are dissolved in 1800 ml of toluene and stirred vigorously together with550 ml (14.6 mol) of formic acid with addition of 10.0 ml (0.56 mol) ofwater. After 18 h, the organic phase is separated off, and the formicacid is extracted with toluene. The combined organic phases are washedsuccessively with water, sat. sodium hydrogencarbonate solution and sat.sodium chloride solution and dried using sodium sulfate. The crudeproduct remaining after removal of the solvent is purified by columnchromatography (SiO₂, toluene:ethyl acetate=4:1), giving (±)-(4aR*,9bS*)-7-ethoxy-6-fluoro-1,4,4a,9b-tetrahydro-2H-dibenzofuran-3-one ascolourless solid.

1.6 (±)-(4aR*,9bS*)-7-Ethoxy-6-fluoro-3-[1-methoxymethylidene]-1,2,3,4,4a,9b-hexahydrodibenzofuran

58.3 g (170 mmol) of methoxymethyltriphenylphosphonium chloride areinitially introduced in 500 ml of THF, and a solution of 19.1 g (170mmol) of potassium tert-butoxide in 200 ml of THF is added at 0° C.After 30 min at this temperature,7-ethoxy-6-fluoro-1,4,4a,9b-tetrahydro-2H-dibenzofuran-3-one as asolution in 300 ml of THF is added, and the batch is stirred at roomtemperature for 17 h. Water is added at 0° C., and the mixture isacidified using 2 N hydrochloric acid. The batch is extracted with MTBE,and the combined extracts are washed with sat. sodium chloride solution.The solution is dried using sodium sulfate and concentrated to dryness.Purification of the crude product by column chromatography (SiO₂,toluene) gives (±)-(4aR*,9bS*)-7-ethoxy-6-fluoro-3-[1-methoxy-methylidene]-1,2,3,4,4a,9b-hexahydrodibenzofuranas colourless solid.

1.7 (±)-(3R*, 4aR*,9bS*-7-Ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-carbaldehydeand (±)-(3S*, 4aR*,9bS*)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-carbaldehyde

8.0 g (28.7 mmol) of (±)-(4aR*,9bS*)-7-ethoxy-6-fluoro-3-[1-methoxy-methylidene]-1,2,3,4,4a,9b-hexahydrodibenzofuranare dissolved in 200 ml of toluene and stirred vigorously at roomtemperature for 18 h together with 30 ml (0.80 mol) of formic acid and0.5 ml (27.8 mmol) of water. The organic phase is separated off andwashed successively with water, sat. sodium hydrogencarbonate solutionand sat. sodium chloride solution. The solution is dried using sodiumsulfate and concentrated to dryness. Purification by columnchromatography (SiO₂, toluene:ethyl acetate=99:1) gives a mixture(64:36) of (±)-(3R*, 4aR*,9bS*)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-carbaldehydeand (±)-(3S*, 4aR*,9bS*)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-carbaldehyde.

1.8 Isomerisation to (±)-(3R*, 4aR*,9bS*)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-carbaldehyde

6.70 g (25.2 mmol) of a mixture (64:36) of (±)-(3R*, 4aR*,9bS*)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-carbaldehydeand (±)-(3S*, 4aR*,9bS*)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-carbaldehydeare dissolved in 170 ml of methanol/THF mixture (5:2), and 0.37 ml (2.50mmol) of aqueous sodium hydroxide solution (20%) is added dropwise.After 1 h at room temperature, the solution is added to water andacidified using 2 N hydrochloric acid. The batch is extracted with MTBE,and the combined organic phases are washed with sat. sodium chloridesolution. The solution is dried using sodium sulfate and concentrated todryness. The crude product from the reaction is used directly for thefollowing steps.

1.9 (±)-(3R*, 4aR*,9bS*)-7-Ethoxy-6-fluoro-3-propenyl-1,2,3,4,4a,9b-hexahydrodibenzofuran

10.0 g (27.0 mmol) of ethyltriphenylphosphonium bromide are initiallyintroduced in 100 ml of THF, and 2.98 g (26.0 mmol) of potassiumtert-butoxide in 40 ml of THF are added at −5° C. After 1 h at thistemperature, 6.50 g (24.6 mmol) of (±)-(3R*, 4aR*,9bS*)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-carbaldehydeas a solution in 60 ml of THF are added dropwise, and the batch isstirred at room temperature for 2 h. The reaction solution is hydrolysedusing water and acidified using 2 N HCl. The mixture is extracted withMTBE, and the combined organic phases are dried using sodium sulfate.The crude product remaining after removal of the solvents is filteredadsorptively (SiO₂, toluene), and the filtrate is concentrated todryness. Recrystallisation of the residue from methanol gives (±)-(3R*,4aR*,9bS*)-7-ethoxy-6-fluoro-3-propenyl)-1,2,3,4,4a,9b-hexahydrodibenzofuranas E/Z isomer mixture.

1.10 (±)-(3R*, 4aR*,9bS*)-7-Ethoxy-6-fluoro-3-propyl-1,2,3,4,4a,9b-hexahydrodibenzofuran

3.50 g (12.7 mmol) of (±)-(3R*, 4aR*,9bS*)-7-ethoxy-6-fluoro-3-propenyl-1,2,3,4,4a,9b-hexahydrodibenzofuranin THF are hydrogenated for 23 h in a hydrogen atmosphere with additionof 1.8 g of Pd/C. After completion of the uptake of hydrogen, thereaction solution is filtered and concentrated to dryness. The residueis filtered adsorptively (SiO₂, toluene:n-heptane=1:1), and the beigesolid obtained is recrystallised repeatedly from isopropanol at roomtemperature, giving (±)-(3R*, 4aR*,9bS*)-7-ethoxy-6-fluoro-3-propyl-1,2,3,4,4a,9b-hexahydrodibenzofuran ascolourless solid (melting point 128° C.).

C 128 l

Δε=−6.0Δn=0.102γ₁=127 mPa·s

¹H-NMR (500 MHz, CHCl₃): δ=6.73 (d, 1H, J=8.0 Hz, 9-H), 6.45 (dd, 1H,J=8.0 Hz, J=6.8 Hz, 8-H), 4.06 (dq, 2H, J=7.0 Hz, J=1.5 Hz, OCH₂CH₃),3.95 (ddd, 1H, J=12.6 Hz, J=11.5 Hz, J=3.5 Hz, 4a-H), 2.74 (ddd, 1H,J=12.6 Hz, J=12.6 Hz, J=2.8 Hz, 9b-H), 2.41-2.37 (m, 1H, 4-H), 2.30-2.26(m, 1H, 1-H), 1.89 (dd, 1H, J=13.8 Hz, J=2.7 Hz, 2-H), 1.58-1.45 (m, 2H,1-H, 3-H), 1.42 (t, 3H, J=7.0 Hz, OCH₂CH₃), 1.39-1.29 (m, 5H, 4-H,CH₂CH₂CH₃), 1.06 (ddd, 1H, J=13.8 Hz, J=12.9 Hz, J=4.0 Hz, 2-H), 0.91(t, 3H, J=6.9 Hz, CH₂CH₂CH₃).

¹⁹F-NMR (235 MHz, CHCl₃): δ=−157.9 (d, 1 F, ⁴J=6.8 Hz).

MS: m/e (%)=278 (100, M+), 235 ([M-Pr]⁺, 49).

2.(±)-(3R*,4aR*,9bS*)-7-Ethoxy-3-(4-ethoxy-2,3-difluorophenyl)-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran2.1 (±)-(4aR*,9bS*)-7-Ethoxy-3-(4-ethoxy-2,3-difluorophenyl)-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-ol

7.94 g (50.2 mmol) of 2,3-difluoroethoxybenzene are initially introducedin 50 ml of THF, and 30.5 ml (48.8 mol) of n-BuLi (15% soln. in hexane)are added at −70° C. After 1 h at this temperature, a solution of 10.0 g(40.0 mmol) of (±)-(4aR*,9bS*)-7-ethoxy-6-fluoro-1,4,4a,9b-tetrahydro-2H-dibenzofuran-3-one in150 ml of THF is metered in. After 4 h, the batch is hydrolysed usingwater and acidified using 4 N HCl. The solution is extracted with MTBE,and the combined organic phases are washed with sat. sodium chloridesolution and dried using sodium sulfate. The crude product remainingafter removal of the solvents under reduced pressure is digested in 500ml of ethanol at 40° C. Filtration gives (±)-(4aR*,9bS*)-7-ethoxy-3-(4-ethoxy-2,3-difluorophenyl)-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-olas colourless solid.

2.2 (±)-(4aR*,9bS*)-7-Ethoxy-3-(4-ethoxy-2,3-difluorophenyl)-6-fluoro-1,2,4a,9b-tetrahydrodibenzofuranand (±)-(4aR*,9bS*)-7-ethoxy-3-(4-ethoxy-2,3-difluorophenyl)-6-fluoro-1,4,4a,9b-tetrahydrodibenzofuran

8.5 g (20.8 mmol) of (±)-(4aR*,9bS*)-7-ethoxy-3-(4-ethoxy-2,3-difluorophenyl)-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-olin 200 ml of toluene are heated on a water separator for 30 min togetherwith 396 mg (2.08 mmol) of p-toluenesulfonic acid monohydrate. Aftercooling, the batch is filtered adsorptively (SiO₂, ethylacetate:n-heptane=4:1), and the filtrate is concentrated to dryness. Theproduct mixture obtained in this way can be used directly for thefollowing reaction.

2.3 (±)-(3R*, 4aR*,9bS*)-7-Ethoxy-3-(4-ethoxy-2,3-difluorophenyl)-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran

7.4 g (about 19.0 mmol) of a mixture of (±)-(4aR*,9bS*)-7-ethoxy-3-(4-ethoxy-2,3-difluorophenyl)-6-fluoro-1,2,4a,9b-tetrahydrodibenzofuranand (±)-(4aR*,9bS*)-7-ethoxy-3-(4-ethoxy-2,3-difluorophenyl)-6-fluoro-1,4,4a,9b-tetrahydrodibenzofuranin 160 ml of ethyl acetate/ethanol mixture (3:1) are hydrogenated at 80°C. in the presence of 3.70 g of Raney nickel and 1.50 g of ion exchanger(weakly H-acidic) under hydrogen pressure (4.4 bar). After 18 h, thecatalyst is filtered off, and the filtrate is concentrated to dryness.The crude product is recrystallised successively from isopropanol,n-heptane and ethanol, giving (±)-(3R*, 4aR*,9bS*)-7-ethoxy-3-(4-ethoxy-2,3-difluorophenyl)-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuranas colourless solid (melting point 126° C.).

C 126 N (99) l

Δε=−12.0Δn=0.138

¹H-NMR (250 MHz, CHCl₃): δ=6.94-6.87 (m, 1H, H_(arom.)), 6.78 (dm, 1H,J=8.0 Hz, H_(arom.)), 6.75-6.67 (m, 1H, H_(arom.)), 6.49 (dd, 1H, J=8.0Hz, J=7.0 Hz, H_(arom.)), 4.17-4.04 (m, 5H, OCH₂CH₃, 4a-H, OCH₂CH₃),3.11-2.86 (m, 2H, 9b-H, 3-H), 2.54-2.37 (m, 2H, H_(aliph.)), 2.20-1.96(m, 2H, H_(aliph.)), 1.63-1.55 (m, 2H, H_(aliph.)), 1.44 (t, 3H, J=7.0Hz, OCH₂CH₃), 1.43 (t, 3H, J=7.0 Hz, OCH₂CH₃).

¹⁹F-NMR (235 MHz, CHCl₃): δ=−142.9 (ddd, 1F, J=13.5 Hz, J=7.4 Hz, J=1.2Hz), −159.2 (ddd, 1F, J=13.5 Hz, J=7.4 Hz, J=1.2 Hz), −159.8 (d, 1 F,J=6.8 Hz).

MS (EI): m/e (%)=392 (39, M⁺), 234 (100).

3.(±)-(3R*,4aR*,9bS*)-7-Ethoxy-6-fluoro-3-vinyl-1,2,3,4,4a,9b-hexahydrodibenzofuran

5.0 g (14.0 mmol) of methyltriphenylphosphonium bromide are initiallyintroduced in 50 ml of THF, and 1.60 g (14.3 mmol) of potassiumtert-butoxide in 20 ml of THF are added at −5° C. After 1 h at thistemperature, 3.40 g (12.9 mmol) of (±)-(3R*, 4aR*,9bS*)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-carbaldehydeas a solution in 30 ml of THF are added dropwise, and the batch isstirred at room temperature for 16 h. The reaction solution ishydrolysed using water and acidified using 2 N HCl. The mixture isextracted with MTBE, and the combined organic phases are washed withsat. sodium chloride solution and dried using sodium sulfate. The crudeproduct remaining after removal of the solvents is purified by columnchromatography (SiO₂, toluene). Further purification was carried out byrepeated recrystallisation from isopropanol, giving (±)-(3R*, 4aR*,9bS*)-7-ethoxy-6-fluoro-3-vinyl-1,2,3,4,4a,9b-hexahydrodibenzofuran ascolourless solid (melting point 141° C.).

C 141 l

¹H-NMR (250 MHz, CHCl₃): δ=6.75 (dm, 1H, J=8.0 Hz, 9-H), 6.46 (dd, 1H,J=8.0 Hz, J=7.0 Hz, 8-H), 5.92-5.78 (m, 1H, H_(vinyl)) 5.11-4.97 (m, 2H,H_(vinyl)), 4.07 (d, 2H, J=7.0 Hz, OCH₂CH₃), 4.05-3.95 (m, 1H, 4a-H),2.83-2.72 (m, 1H, 9b-H), 2.47-2.18 (m, 3H, H_(aliph.)), 1.97-1.87 (m,1H, H_(aliph.)), 1.80-1.67 (m, 1H, H_(aliph.)), 1.53-1.18 (m, 5H, J=7.0Hz, H_(aliph.), OCH₂CH₃).

¹⁹F-NMR (235 MHz, CHCl₃): δ=−157.6 (d, 1 F, ⁴J=6.8 Hz).

MS (EI): m/e (%)=262 (81, M⁺), 206 (100, [M-Et-Vn]⁺).

4. (±)-(3R*, 4aR*,9bS*)-7-Ethoxy-6-fluoro-3-((E)-propenyl)-1,2,3,4,4a,9b-hexahydrodibenzofuran4.1 Isomerisation to (±)-(3R*, 4aR*,9bS*)-7-ethoxy-6-fluoro-3-((E)-propenyl)-1,2,3,4,4a,9b-hexahydrodibenzofuran

6.0 g (about 21.7 mmol) of (E/Z) isomer mixture of (±)-(3R*, 4aR*,9bS*)-7-ethoxy-6-fluoro-3-propenyl-1,2,3,4,4a,9b-hexahydrodibenzofuran(see 1.9) are refluxed in 60 ml of toluene together with 1.15 g (7.0mmol) of benzene-sulfinic acid sodium salt and 21.4 ml of 1 Nhydrochloric acid. After 1 h, the mixture is added to water, and theorganic phase is separated off. The aqueous phase is extracted withMTBE, and the combined organic phases are washed with sat. sodiumchloride solution. The solution is dried using sodium sulfate andconcentrated to dryness. Repeated recrystallisation from isopropanolgives (±)-(3R*, 4aR*,9bS*)-7-ethoxy-6-fluoro-3-((E)-propenyl)-1,2,3,4,4a,9b-hexahydrodibenzofuranas colourless solid (melting point 145° C.).

C 145 l

Δε=−6.0Δn=0.110

¹H-NMR (250 MHz, CHCl₃): δ=6.74 (dm, 1H, J=8.0 Hz, 9-H), 6.46 (dd, 1H,J=8.0 Hz, J=7.0 Hz, 8-H), 5.54-5.38 (m, 2H, H_(vinyl)), 4.07 (q, 2H,J=7.0 Hz, OCH₂CH₃), 4.04-3.92 (m, 1H, 4a-H), 2.81-2.70 (m, 1H, 9b-H),2.42-2.11 (m, 3H, H_(aliph.)), 1.91-1.82 (m, 1H, H_(aliph.)), 1.76-1.62(m, 4H, J=4.8 Hz, H_(aliph.), CH═CHCH₃), 1.52-1.14 (m, 5H, J=7.0 Hz,H_(aliph.), OCH₂CH₃).

¹⁹F-NMR (235 MHz, CHCl₃): δ=−159.1 (d, 1F, ⁴J=6.8 Hz).

MS (EI): m/e (%)=276 (72, M⁺), 206 (100, [M-Et-C₃H₅]⁺).

5. (±)-(3R*, 4aR*,9bS*)-7-Ethoxy-6-fluoro-3-pentyl-1,2,3,4,4a,9b-hexahydrodibenzofuran 5.1(±)-(3R*,4aR*,9bS-7-Ethoxy-6-fluoro-3-((E)-pent-1-enyl)-1,2,3,4,4a,9b-hexahydrodibenzofuranand (±)-(3R*,4aR*,9bS-7-ethoxy-6-fluoro-3-((Z)-pent-1-enyl)-1,2,3,4,4a,9b-hexahydrodibenzofuran

8.98 g (22.5 mmol) of butyltriphenylphosphonium bromide are initiallyintroduced in 100 ml of THF, and 2.58 g (23.0 mmol) of potassiumtert-butoxide in 40 ml of THF are added at −5° C. After 1 h at thistemperature, 5.50 g (20.8 mmol) of (±)-(3R*, 4aR*,9bS-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-carbaldehydeas a solution in 60 ml of THF are added dropwise, and the batch isstirred at room temperature for 2 h. The reaction solution is hydrolysedusing water and acidified using 2 N HCl. The mixture is extracted withMTBE, and the combined organic phases are washed with sat. sodiumchloride solution and dried using sodium sulfate. The crude productremaining after removal of the solvents is purified by columnchromatography (SiO₂, toluene). The E/Z isomer mixture obtained in thisway can be used directly for the following reaction.

5.2 (±)-(3R*, 4aR*,9bS*)-7-Ethoxy-6-fluoro-3-pentyl-1,2,3,4,4a,9b-hexahydrodibenzofuran

5.1 g (about 10.7 mmol) of (E/Z) isomer mixture of (±)-(3R*, 4aR*,9bS*)-7-ethoxy-6-fluoro-3-pent-1-enyl-1,2,3,4,4a,9b-hexahydrodibenzofuranin 50 ml of THF are hydrogenated in a hydrogen atmosphere with additionof 5.0 g of Pd/C (5% Pd). After completion of the uptake of hydrogen (37h), the reaction solution is filtered and concentrated to dryness. Theresidue is filtered adsorptively (SiO₂, toluene), and the beige solidobtained is re-crystallised repeatedly from isopropanol at roomtemperature, giving (±)-(3R*, 4aR*,9bS*)-7-ethoxy-6-fluoro-3-pentyl-1,2,3,4,4a,9b-hexahydro-dibenzofuran ascolourless solid (melting point 118° C.).

C 118 l

Δε=−5.4Δn=0.104γ₁=172 mPa·s

¹H-NMR (250 MHz, CHCl₃): δ=6.74 (dm, 1H, J=8.0 Hz, 9-H), 6.45 (dd, 1H,J=8.0 Hz, J=7.0 Hz, 8-H), 4.07 (q, 2H, J=7.0 Hz, OCH₂CH₃), 4.01-3.90 (m,1H, 4a-H), 2.80-2.69 (m, 1H, 9b-H), 2.43-2.36 (m, 1H, H_(aliph.)), 2.29(dm, 1H, J=12.5 Hz, H_(aliph.)), 1.90 (dd, 1H, J=13.1 Hz, J=2.7 Hz,H_(aliph.)), 1.50-1.20 (m, 14H, H_(aliph.)), 1.16-0.98 (m, 1H,H_(aliph.)), 0.90 (t, 3H, J=7.0 Hz, OCH₂CH₃).

¹⁹F-NMR (235 MHz, CHCl₃): δ=−160.1 (d, 1F, ⁴J=7.1 Hz).

MS (EI): m/e (%)=306 (100, M⁺), 235 (100, [M-C₅H₁₁]⁺).

6.(±)-(3R*,4aR*,9bS*)-7-Butoxy-6-fluoro-3-(4-propylcyclohexyl)-1,2,3,4,4a,9b-hexahydrodibenzofuran6.1 4-(4-Butoxy-2,3-difluorophenyl)-4′-propylbicyclohexyl-4-ol

31.0 g (0.17 mol) of 1-butoxy-2,3-difluorobenzene are initiallyintroduced in 200 ml of THF, and 100 ml (0.16 mol) of n-BuLi (15% soln.in hexane) are added at −70° C. After 2 h at this temperature, asolution of 35.6 g (0.16 mol) of 4′-propylbicyclohexyl-4-one in 200 mlof THF is metered in, and the batch is stirred for 2.5 h. The reactionmixture is hydrolysed with ice-cooling and acidified using 2 N HCl. Thesolution is extracted with MTBE, and the combined organic phases arewashed with sat. sodium chloride solution and dried using sodiumsulfate. The solution is concentrated to dryness, and the crude product(66.3 g of yellow solid) is used directly for the following reaction.6.2 4-(4-Butoxy-2,3-difluorophenyl)-4′-propylbicyclohexyl-3-ene

66.3 g (about 0.16 mol) of crude4-(4-butoxy-2,3-difluorophenyl)-4′-propylbicyclohexyl-4-ol in 200 ml oftoluene are heated on a water separator for 2 h together with 3.04 g(16.0 mmol) of p-toluenesulfonic acid monohydrate. After cooling, thebatch is washed successively with water, sat. sodium hydrogencarbonatesolution and sat. sodium chloride solution. The solution is dried usingsodium sulfate and concentrated to dryness. The crude product (60.7 g oforange oil) is crystallised from ethanol, giving4-(4-butoxy-2,3-difluorophenyl)-4′-propylbicyclohexyl-3-ene as yellowsolid.

6.3 4-(4-Butoxy-2,3-difluorophenyl)-4′-propylbicyclohexyl-3-ol

110 ml (0.11 mol) of borane/THF complex (1 M solution) are added at −5°C. to a solution of 31.4 g (80.4 mmol) of4-(4-butoxy-2,3-difluorophenyl)-4′-propylbicyclohexyl-3-ene in 320 ml ofTHF, and the reaction mixture is stirred at room temperature for 3 h. 20ml (0.35 mol) of ethanol, 50 ml (0.2 mol) of aqueous sodium hydroxidesolution (4 M) and 28 ml (0.32 mol) of aqueous hydrogen peroxide soln.(35%) are added successively to the batch, during which the internaltemperature does not exceed 47° C. (ice bath). When the addition iscomplete, the mixture is refluxed for 2 h, and the solution is cooled,added to water and stirred vigorously. The organic phase is separatedoff, and the aqueous phase is extracted with MTBE. The combined organicphases are washed with sat. sodium chloride solution and dried usingsodium sulfate. The solution is concentrated to dryness, and the crudeproduct (32 g) is purified by column chromatography (SiO₂, toluene →toluene:ethyl acetate=8:2), giving4-(4-butoxy-2,3-difluorophenyl)-4′-propylbicyclohexyl-3-ol as colourlesssolid.

6.4(±)-(3R*,4aR*,9bS*)-7-Butoxy-6-fluoro-3-(4-propylcyclohexyl)-1,2,3,4,4a,9b-hexahydrodibenzofuran

5.40 g (135 mmol) of sodium hydride (60% suspension in mineral oil) arewashed repeatedly with n-pentane and suspended in 400 ml of toluene. Thesuspension is heated to 90° C., and a solution of 17.5 g (42.8 mmol) of4-(4-butoxy-2,3-difluorophenyl)-4′-propylbicyclohexyl-3-ol in 100 ml ofDMF is metered in slowly. The batch is stirred at 90° C. for 20 h,cooled and hydrolysed using water. The mixture is neutralised byaddition of 2 N hydrochloric acid, and the organic phase is separatedoff. The aqueous phase is extracted with toluene, and the combinedorganic phases are washed with sat. sodium chloride solution. Thesolution is dried using sodium sulfate and concentrated to dryness underreduced pressure. The crude product obtained is recrystallised fromethanol at 5° C., giving (±)-(3R*, 4aR*,9bS*-7-butoxy-6-fluoro-3-(4-propylcyclohexyl)-1,2,3,4,4a,9b-hexahydrodibenzofuranas colourless solid (melting point 105° C.).

C 105 Sm_(A) 154 N 166 l

Δε=−5.6Δn=0.114γ₁=974 mPa·s

¹H-NMR (250 MHz, CHCl₃): δ=6.73 (dm, 1H, J=8.0 Hz, 9-H), 6.45 (dd, 1H,J=8.0 Hz, J=7.0 Hz, 8-H), 3.99 (t, 3H, J=6.9 Hz, OCH₂CH₂), 3.98-3.88 (m,1H, 4a-H), 2.77-2.66 (m, 1H, H_(aliph.)), 2.40-2.26 (m, 2H, H_(aliph.)),1.90-1.69 (m, 9H, H_(aliph.)), 1.65-1.02 (m, 13H, H_(aliph.)), 0.96 (t,3H, J=7.4 Hz, Me), 0.88 (t, 3H, J=7.2 Hz, Me).

¹⁹F-NMR (235 MHz, CHCl₃): δ=158.2 (d, 1 F, j=6.8 Hz).

MS (EI): m/e (%)=388 (100, M⁺).

7.(±)-(3R*,4aR*,9bS*)-(±)-(3R*,4aR*,9bS*)-7-Ethoxy-6-fluoro-3-(4-vinyl-cyclohexyl)-1,2,3,4,4a,9b-hexahydrodibenzofuran7.14-(1,4-Dioxaspiro[4.5]dec-8-yl)-1-(4-ethoxy-2,3-difluorophenyl)cyclo-hexanol

99.5 g (0.63 mol) of 2,3-difluoroethoxybenzene are initially introducedin 800 ml of THF, and 384 ml (0.63 mol) of n-BuLi (15% soln. in hexane)are added at −70° C. After 30 min at this temperature, a solution of 150g (0.63 mol) of 4-(1,4-dioxaspiro[4.5]dec-8-yl)cyclohexanone in 700 mlof THF is metered in, and the batch is stirred for 30 min. The reactionmixture is warmed to 0° C. and hydrolysed using 2 N HCl. The solution isextracted with MTBE, and the combined organic phases are washed withsat. sodium chloride solution and dried using sodium sulfate. The crudeproduct remaining after removal of the solvents under reduced pressureis used directly for the next reaction.

7.28-[4-(4-Ethoxy-2,3-difluorophenyl)cyclohex-3-enyl]-1,4-dioxaspiro[4.5]decane

250 g of crude4-(1,4-dioxaspiro[4.5]dec-8-yl)-1-(4-ethoxy-2,3-difluorophenyl)cyclohexanolin 1000 ml of toluene are heated on a water separator for 3 h togetherwith 80.0 ml (1.43 mol) of ethylene glycol with addition of 12.0 g (0.06mol) of p-toluenesulfonic acid monohydrate. After cooling, the batch iswashed successively with water, sat. sodium hydrogencarbonate solutionand sat. sodium chloride solution. The solution is dried using sodiumsulfate and concentrated to dryness. The crude product is crystallisedfrom acetonitrile, giving8-[4-(4-ethoxy-2,3-difluorophenyl)cyclohex-3-enyl]-1,4-dioxaspiro[4.5]decaneas colourless solid.

7.35-(1,4-Dioxaspiro[4.5]dec-8-yl)-2-(4-ethoxy-2,3-difluorophenyl)-cyclohexanol

550 ml (0.55 mol) of borane/THF complex (1 M solution) are added at −5°C. to a solution of 154.0 g (0.41 mol) of8-[4-(4-ethoxy-2,3-difluorophenyl)-cyclohex-3-enyl]-1,4-dioxaspiro[4.5]decanein 1500 ml of THF, and the reaction mixture is stirred at roomtemperature for 3 h. 99 ml (1.7 mol) of ethanol, 250 ml (1.0 mol) ofaqueous sodium hydroxide solution (16%) and 140 ml (1.6 mol) of aqueoushydrogen peroxide soln. (35%) are added successively to the batch,during which the internal temperature does not exceed 46° C. (ice bath).When the addition is complete, the mixture is refluxed for 2 h, and thesolution is cooled, added to water and stirred vigorously. The organicphase is separated off, and the aqueous phase is extracted with MTBE.The combined organic phases are washed with sat. sodium chloridesolution and dried using sodium sulfate. The solution is concentrated todryness, and the crude product is purified by column chromatography(SiO₂, toluene:ethyl acetate=8:2), giving5-(1,4-dioxaspiro[4.5]dec-8-yl)-2-(4-ethoxy-2,3-difluorophenyl)cyclohexanolas colourless, viscous oil.

7.4(±)-(3R*,4aR*,9bS*)-3-(1,4-Dioxaspiro[4.5]dec-8-yl)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran

30.0 g (0.75 mol) of sodium hydride (60% suspension in mineral oil) arewashed repeatedly with n-pentane and suspended in 2500 ml of toluene.The suspension is heated to 90° C., and a solution of 101.5 g (0.26 mol)of5-(1,4-dioxaspiro[4.5]dec-8-yl)-2-(4-ethoxy-2,3-difluorophenyl)cyclohexanolin 500 ml of DMF is metered in slowly. The batch is stirred at 90° C.for 20 h, cooled and hydrolysed using water. The mixture is neutralisedby addition of 2 N hydrochloric acid, and the organic phase is separatedoff. The aqueous phase is extracted with toluene, and the combinedorganic phases are washed with sat. sodium chloride solution. Thesolution is dried using sodium sulfate and concentrated to dryness underreduced pressure. The crude product obtained is firstly purified bycolumn chromatography (SiO₂, toluene:ethyl acetate=8:2) and thenrecrystallised successively from toluene and toluene:ethanol (3:1),giving(±)-(3R*,4aR*,9bS*)-3-(1,4-dioxaspiro[4.5]dec-8-yl)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuranas colourless, crystalline solid.

7.5(±)-4-((3R*,4aR*,9bS*)-7-Ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-yl)cyclohexanone

13.3 g (35.3 mmol) of(±)-(3R*,4aR*,9bS*)-3-(1,4-dioxaspiro[4.5]dec-8-yl)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuranare dissolved in 200 ml of toluene and stirred vigorously together with40 ml (1.06 mol) of formic acid with addition of 1.0 ml (55.6 mmol) ofwater. After 18 h, the organic phase is separated off, and the formicacid is extracted with toluene. The combined organic phases are washedsuccessively with water, sat. sodium hydrogencarbonate solution and sat.sodium chloride solution and dried using sodium sulfate. The crudeproduct remaining after removal of the solvent is purified by columnchromatography (SiO₂, toluene:ethyl acetate=4:1), giving(±)-4-((3R*,4aR*,9bS*)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-yl)cyclohexanoneas colourless solid.

7.6(±)-(3R*,4aR*,9bS*)-7-Ethoxy-6-fluoro-3-(4-methoxymethylene-cyclohexyl)-1,2,3,4,4a,9b-hexahydrodibenzofuran

14.1 g (41.3 mmol) of methoxymethyltriphenylphosphonium chloride areinitially introduced in 250 ml of THF, and a solution of 4.6 g (41.0mmol) of potassium tert-butoxide in 100 ml of THF is added at 0° C.After 30 min at this temperature,(±)-4-((3R*,4aR*,9bS*)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-yl)cyclohexanoneas a solution in 150 ml of THF is added, and the batch is stirred atroom temperature for 17 h. The mixture is treated with water at 0° C.and acidified using 2 N hydrochloric acid. The batch is extracted withMTBE, and the combined extracts are washed with sat. sodium chloridesolution. The solution is dried using sodium sulfate and concentrated todryness. Purification of the crude product by column chromatography(SiO₂, toluene:ethyl acetate=95:5) gives(±)-(3R*,4aR*,9bS*)-7-ethoxy-6-fluoro-3-(4-methoxymethylene-cyclohexyl)-1,2,3,4,4a,9b-hexahydrodibenzofuranas colourless solid.

7.7(±)-4-((3R*,4aR*,9bS*)-7-Ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydro-dibenzofuran-3-yl)cyclohexanecarbaldehyde

10.0 g (27.7 mmol) of(±)-(3R*,4aR*,9bS*)-7-ethoxy-6-fluoro-3-(4-methoxy-methylenecyclohexyl)-1,2,3,4,4a,9b-hexahydrodibenzofuranare dissolved in 400 ml of toluene and stirred vigorously at roomtemperature for 18 h together with 30 ml (0.80 mol) of formic acid and1.0 ml (55.6 mmol) of water. The organic phase is separated off andwashed successively with water, sat. sodium hydrogencarbonate solutionand sat. sodium chloride solution. The solution is dried using sodiumsulfate and concentrated to dryness.

The residue is dissolved in 250 ml of methanol/THF mixture (5:2), and0.44 ml (3.0 mmol) of aqueous sodium hydroxide solution (20%) is addeddropwise. After 3 h at room temperature, the solution is added to waterand acidified using 2 N hydrochloric acid. The batch is extracted withMTBE, and the combined organic phases are washed with sat. sodiumchloride solution. The solution is dried using sodium sulfate andconcentrated to dryness. The crude product from the reaction is useddirectly for the following steps.

7.8(±)-(3R*,4aR*,9bS*)-7-Ethoxy-6-fluoro-3-(4-vinylcyclohexyl)-1,2,3,4,4a,9b-hexahydrodibenzofuran

9.65 g (27.0 mmol) of methyltriphenylphosphonium bromide are initiallyintroduced in 100 ml of THF, and 3.09 g (27.0 mmol) of potassiumtert-butoxide in 60 ml of THF are added at −5° C. After 1 h at thistemperature, 8.40 g (about 24 mmol) of crude(±)-4-((3R*,4aR*,9bS*)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-yl)cyclohexanecarbaldehydeas a solution in 90 ml of THF are added dropwise, and the batch isstirred at room temperature for 3 h. The reaction solution is hydrolysedusing water and acidified using 2 N HCl. The mixture is extracted withMTBE, and the combined organic phases are dried using sodium sulfate.The crude product remaining after removal of the solvents is filteredadsorptively (SiO₂, toluene), and the filtrate is concentrated todryness. Repeated recrystallisation of the residue from ethanol gives(±)-(3R*,4aR*,9bS*)-7-ethoxy-6-fluoro-3-(4-vinylcyclohexyl)-1,2,3,4,4a,9b-hexahydrodibenzofuranas colourless solid (m.p. 132° C.).

C 132 N 157 l

Δε=−6.7Δn=0.121γ₁=911 mPa·s

¹H-NMR (250 MHz, CHCl₃): δ=6.74 (dm, 1H, J=7.8 Hz, 9-H), 6.45 (dd, 1H,J=8.0 Hz, J=7.0 Hz, 8-H), 5.84-5.71 (m, 1H, H_(vinyl.)), 5.00-4.86 (m,2H, H_(vinyl.)), 4.07 (q, 2H, J=7.0 Hz, OCH₂CH₃), 4.00-3.89 (m, 1H,4a-H), 2.78-2.67 (m, 1H, H_(aliph.)), 2.41-2.27 (m, 2H, H_(aliph.)),1.91-1.74 (m, 7H, H_(aliph.)), 1.67-1.63 (m, 1H, H_(aliph.)), 1.42 (t,3H, J=7.0 Hz, OCH₂CH₃), 1.36-1.06 (m, 7H, H_(aliph.))

MS (EI): m/e (%)=344 (100, M⁺).

The following compounds are obtained analogously to the examplesindicated using the corresponding precursors (Examples 1-1014; Tables 1to 4, data Table 5):

Analogously to Example 1: Examples 8 to 62:

Analogously to Example 1: Examples 63 to 117:

Analogously to Examples 3, 4 and 5: Examples 118 to 173:

Analogously to Examples 3, 4 and 5: Examples 173 to 227:

TABLE 1

Ex. R¹ R² 8 CH₃ H 9 CH₃ CH₃ 10 CH₃ C₂H₅ 11 CH₃ n-C₃H₇ 12 CH₃ n-C₄H₉ 13CH₃ n-C₅H₁₁ 14 CH₃ n-C₆H₁₃ 15 CH₃ n-C₇H₁₅ 16 C₂H₅ H 17 C₂H₅ CH₃ 18 C₂H₅C₂H₅ 19 C₂H₅ n-C₃H₇ 20 C₂H₅ n-C₄H₉ 21 C₂H₅ n-C₅H₁₁ 22 C₂H₅ n-C₆H₁₃ 23C₂H₅ n-C₇H₁₅ 24 n-C₃H₇ H 25 n-C₃H₇ CH₃ 26 n-C₃H₇ C₂H₅ 27 n-C₃H₇ n-C₄H₉28 n-C₃H₇ n-C₅H₁₁ 29 n-C₃H₇ n-C₆H₁₃ 30 n-C₃H₇ n-C₇H₁₅ 31 n-C₄H₉ H 32n-C₄H₉ CH₃ 33 n-C₄H₉ C₂H₅ 34 n-C₄H₉ n-C₃H₇ 35 n-C₄H₉ n-C₄H₉ 36 n-C₄H₉n-C₅H₁₁ 37 n-C₄H₉ n-C₆H₁₃ 38 n-C₄H₉ n-C₇H₁₅ 39 n-C₅H₁₁ H 40 n-C₅H₁₁ CH₃41 n-C₅H₁₁ C₂H₅ 42 n-C₅H₁₁ n-C₃H₇ 43 n-C₅H₁₁ n-C₄H₉ 44 n-C₅H₁₁ n-C₅H₁₁45 n-C₅H₁₁ n-C₆H₁₃ 46 n-C₅H₁₁ n-C₇H₁₅ 47 n-C₆H₁₃ H 48 n-C₆H₁₃ CH₃ 49n-C₆H₁₃ C₂H₅ 50 n-C₆H₁₃ n-C₃H₇ 51 n-C₆H₁₃ n-C₄H₉ 52 n-C₆H₁₃ n-C₅H₁₁ 53n-C₆H₁₃ n-C₆H₁₃ 54 n-C₆H₁₃ n-C₇H₁₅ 55 n-C₇H₁₅ H 56 n-C₇H₁₅ CH₃ 57n-C₇H₁₅ C₂H₅ 58 n-C₇H₁₅ n-C₃H₇ 59 n-C₇H₁₅ n-C₄H₉ 60 n-C₇H₁₅ n-C₅H₁₁ 61n-C₇H₁₅ n-C₆H₁₃ 62 n-C₇H₁₅ n-C₇H₁₅ 63 CH₃ H 64 CH₃ CH₃ 65 CH₃ C₂H₅ 66CH₃ n-C₃H₇ 67 CH₃ n-C₄H₉ 68 CH₃ n-C₅H₁₁ 69 CH₃ n-C₆H₁₃ 70 CH₃ n-C₇H₁₅ 71C₂H₅ H 72 C₂H₅ CH₃ 73 C₂H₅ C₂H₅ 74 C₂H₅ n-C₃H₇ 75 C₂H₅ n-C₄H₉ 76 C₂H₅n-C₅H₁₁ 77 C₂H₅ n-C₆H₁₃ 78 C₂H₅ n-C₇H₁₅ 79 n-C₃H₇ H 80 n-C₃H₇ CH₃ 81n-C₃H₇ C₂H₅ 82 n-C₃H₇ n-C₄H₉ 83 n-C₃H₇ n-C₅H₁₁ 84 n-C₃H₇ n-C₆H₁₃ 85n-C₃H₇ n-C₇H₁₅ 86 n-C₄H₉ H 87 n-C₄H₉ CH₃ 88 n-C₄H₉ C₂H₅ 89 n-C₄H₉ n-C₃H₇90 n-C₄H₉ n-C₄H₉ 91 n-C₄H₉ n-C₅H₁₁ 92 n-C₄H₉ n-C₆H₁₃ 93 n-C₄H₉ n-C₇H₁₅94 n-C₅H₁₁ H 95 n-C₅H₁₁ CH₃ 96 n-C₅H₁₁ C₂H₅ 97 n-C₅H₁₁ n-C₃H₇ 98 n-C₅H₁₁n-C₄H₉ 99 n-C₅H₁₁ n-C₅H₁₁ 100 n-C₅H₁₁ n-C₆H₁₃ 101 n-C₅H₁₁ n-C₇H₁₅ 102n-C₆H₁₃ H 103 n-C₆H₁₃ CH₃ 104 n-C₆H₁₃ C₂H₅ 105 n-C₆H₁₃ n-C₃H₇ 106n-C₆H₁₃ n-C₄H₉ 107 n-C₆H₁₃ n-C₅H₁₁ 108 n-C₆H₁₃ n-C₆H₁₃ 109 n-C₆H₁₃n-C₇H₁₅ 110 n-C₇H₁₅ H 111 n-C₇H₁₅ CH₃ 112 n-C₇H₁₅ C₂H₅ 113 n-C₇H₁₅n-C₃H₇ 114 n-C₇H₁₅ n-C₄H₉ 115 n-C₇H₁₅ n-C₅H₁₁ 116 n-C₇H₁₅ n-C₆H₁₃ 117n-C₇H₁₅ n-C₇H₁₅ 118 CH₃ H 119 CH₃ CH₃ 120 CH₃ C₂H₅ 121 CH₃ n-C₃H₇ 122CH₃ n-C₄H₉ 123 CH₃ n-C₅H₁₁ 124 CH₃ n-C₆H₁₃ 125 CH₃ n-C₇H₁₅ 126 C₂H₅ H127 C₂H₅ CH₃ 128 C₂H₅ C₂H₅ 129 C₂H₅ n-C₃H₇ 130 C₂H₅ n-C₄H₉ 131 C₂H₅n-C₅H₁₁ 132 C₂H₅ n-C₆H₁₃ 133 C₂H₅ n-C₇H₁₅ 134 n-C₃H₇ H 135 n-C₃H₇ CH₃136 n-C₃H₇ C₂H₅ 137 n-C₃H₇ n-C₄H₉ 138 n-C₃H₇ n-C₅H₁₁ 139 n-C₃H₇ n-C₆H₁₃140 n-C₃H₇ n-C₇H₁₅ 141 n-C₄H₉ H 142 n-C₄H₉ CH₃ 143 n-C₄H₉ C₂H₅ 144n-C₄H₉ n-C₃H₇ 145 n-C₄H₉ n-C₄H₉ 146 n-C₄H₉ n-C₅H₁₁ 147 n-C₄H₉ n-C₆H₁₃148 n-C₄H₉ n-C₇H₁₅ 149 n-C₅H₁₁ H 150 n-C₅H₁₁ CH₃ 151 n-C₅H₁₁ C₂H₅ 152n-C₅H₁₁ n-C₃H₇ 153 n-C₅H₁₁ n-C₄H₉ 154 n-C₅H₁₁ n-C₅H₁₁ 155 n-C₅H₁₁n-C₆H₁₃ 156 n-C₅H₁₁ n-C₇H₁₅ 157 n-C₆H₁₃ H 158 n-C₆H₁₃ CH₃ 159 n-C₆H₁₃C₂H₅ 160 n-C₆H₁₃ n-C₃H₇ 161 n-C₆H₁₃ n-C₄H₉ 162 n-C₆H₁₃ n-C₅H₁₁ 163n-C₆H₁₃ n-C₆H₁₃ 164 n-C₆H₁₃ n-C₇H₁₅ 165 n-C₇H₁₅ H 166 n-C₇H₁₅ CH₃ 167n-C₇H₁₅ C₂H₅ 168 n-C₇H₁₅ n-C₃H₇ 169 n-C₇H₁₅ n-C₄H₉ 170 n-C₇H₁₅ n-C₅H₁₁171 n-C₇H₁₅ n-C₆H₁₃ 172 n-C₇H₁₅ n-C₇H₁₅ 173 CH₃ H 174 CH₃ CH₃ 175 CH₃C₂H₅ 176 CH₃ n-C₃H₇ 177 CH₃ n-C₄H₉ 178 CH₃ n-C₅H₁₁ 179 CH₃ n-C₆H₁₃ 180CH₃ n-C₇H₁₅ 181 C₂H₅ H 182 C₂H₅ CH₃ 183 C₂H₅ C₂H₅ 184 C₂H₅ n-C₃H₇ 185C₂H₅ n-C₄H₉ 186 C₂H₅ n-C₅H₁₁ 187 C₂H₅ n-C₆H₁₃ 188 C₂H₅ n-C₇H₁₅ 189n-C₃H₇ H 190 n-C₃H₇ CH₃ 191 n-C₃H₇ C₂H₅ 192 n-C₃H₇ n-C₄H₉ 193 n-C₃H₇n-C₅H₁₁ 194 n-C₃H₇ n-C₆H₁₃ 195 n-C₃H₇ n-C₇H₁₅ 196 n-C₄H₉ H 197 n-C₄H₉CH₃ 198 n-C₄H₉ C₂H₅ 199 n-C₄H₉ n-C₃H₇ 200 n-C₄H₉ n-C₄H₉ 201 n-C₄H₉n-C₅H₁₁ 202 n-C₄H₉ n-C₆H₁₃ 203 n-C₄H₉ n-C₇H₁₅ 204 n-C₅H₁₁ H 205 n-C₅H₁₁CH₃ 206 n-C₅H₁₁ C₂H₅ 207 n-C₅H₁₁ n-C₃H₇ 208 n-C₅H₁₁ n-C₄H₉ 209 n-C₅H₁₁n-C₅H₁₁ 210 n-C₅H₁₁ n-C₆H₁₃ 211 n-C₅H₁₁ n-C₇H₁₅ 212 n-C₆H₁₃ H 213n-C₆H₁₃ CH₃ 214 n-C₆H₁₃ C₂H₅ 215 n-C₆H₁₃ n-C₃H₇ 216 n-C₆H₁₃ n-C₄H₉ 217n-C₆H₁₃ n-C₅H₁₁ 218 n-C₆H₁₃ n-C₆H₁₃ 219 n-C₆H₁₃ n-C₇H₁₅ 220 n-C₇H₁₅ H221 n-C₇H₁₅ CH₃ 222 n-C₇H₁₅ C₂H₅ 223 n-C₇H₁₅ n-C₃H₇ 224 n-C₇H₁₅ n-C₄H₉225 n-C₇H₁₅ n-C₅H₁₁ 226 n-C₇H₁₅ n-C₆H₁₃ 227 n-C₇H₁₅ n-C₇H₁₅

Analogously to Example 2: Examples 228 to 282:

Analogously to Example 2: Examples 283 to 337:

Analogously to Example 2: Examples 338 to 392:

Analogously to Example 2: Examples 393 to 447:

Analogously to Example 2: Examples 448 to 502:

Analogously to Example 2: Examples 503 to 557:

Analogously to Example 2: Examples 558 to 612:

Analogously to Example 2: Examples 613 to 667:

TABLE 2

Ex. R¹ R² 228 CH₃ H 229 CH₃ CH₃ 230 CH₃ C₂H₅ 231 CH₃ n-C₃H₇ 232 CH₃n-C₄H₉ 233 CH₃ n-C₅H₁₁ 234 CH₃ n-C₆H₁₃ 235 CH₃ n-C₇H₁₅ 236 C₂H₅ H 237C₂H₅ CH₃ 238 C₂H₅ C₂H₅ 239 C₂H₅ n-C₃H₇ 240 C₂H₅ n-C₄H₉ 241 C₂H₅ n-C₅H₁₁242 C₂H₅ n-C₆H₁₃ 243 C₂H₅ n-C₇H₁₅ 244 n-C₃H₇ H 245 n-C₃H₇ CH₃ 246 n-C₃H₇C₂H₅ 247 n-C₃H₇ n-C₄H₉ 248 n-C₃H₇ n-C₅H₁₁ 249 n-C₃H₇ n-C₆H₁₃ 250 n-C₃H₇n-C₇H₁₅ 251 n-C₄H₉ H 252 n-C₄H₉ CH₃ 253 n-C₄H₉ C₂H₅ 254 n-C₄H₉ n-C₃H₇255 n-C₄H₉ n-C₄H₉ 256 n-C₄H₉ n-C₅H₁₁ 257 n-C₄H₉ n-C₆H₁₃ 258 n-C₄H₉n-C₇H₁₅ 259 n-C₅H₁₁ H 260 n-C₆H₁₁ CH₃ 261 n-C₅H₁₁ C₂H₅ 262 n-C₅H₁₁n-C₃H₇ 263 n-C₅H₁₁ n-C₄H₉ 264 n-C₅H₁₁ n-C₅H₁₁ 265 n-C₅H₁₁ n-C₆H₁₃ 266n-C₅H₁₁ n-C₇H₁₅ 267 n-C₆H₁₃ H 268 n-C₆H₁₃ CH₃ 269 n-C₆H₁₃ C₂H₅ 270n-C₆H₁₃ n-C₃H₇ 271 n-C₆H₁₃ n-C₄H₉ 272 n-C₆H₁₃ n-C₅H₁₁ 273 n-C₆H₁₃n-C₆H₁₃ 274 n-C₆H₁₃ n-C₇H₁₅ 275 n-C₇H₁₅ H 276 n-C₇H₁₅ CH₃ 277 n-C₇H₁₅C₂H₅ 278 n-C₇H₁₅ n-C₃H₇ 279 n-C₇H₁₅ n-C₄H₉ 280 n-C₇H₁₅ n-C₅H₁₁ 281n-C₇H₁₅ n-C₆H₁₃ 282 n-C₇H₁₅ n-C₇H₁₅ 283 CH₃ H 284 CH₃ CH₃ 285 CH₃ C₂H₅286 CH₃ n-C₃H₇ 287 CH₃ n-C₄H₉ 288 CH₃ n-C₅H₁₁ 289 CH₃ n-C₆H₁₃ 290 CH₃n-C₇H₁₅ 291 C₂H₅ H 292 C₂H₅ CH₃ 293 C₂H₅ C₂H₅ 294 C₂H₅ n-C₃H₇ 295 C₂H₅n-C₄H₉ 296 C₂H₅ n-C₅H₁₁ 297 C₂H₅ n-C₆H₁₃ 298 C₂H₅ n-C₇H₁₅ 299 n-C₃H₇ H300 n-C₃H₇ CH₃ 301 n-C₃H₇ C₂H₅ 302 n-C₃H₇ n-C₄H₉ 303 n-C₃H₇ n-C₅H₁₁ 304n-C₃H₇ n-C₆H₁₃ 305 n-C₃H₇ n-C₇H₁₅ 306 n-C₄H₉ H 307 n-C₄H₉ CH₃ 308 n-C₄H₉C₂H₅ 309 n-C₄H₉ n-C₃H₇ 310 n-C₄H₉ n-C₄H₉ 311 n-C₄H₉ n-C₅H₁₁ 312 n-C₄H₉n-C₆H₁₃ 313 n-C₄H₉ n-C₇H₁₅ 314 n-C₅H₁₁ H 315 n-C₅H₁₁ CH₃ 316 n-C₆H₁₁C₂H₅ 317 n-C₅H₁₁ C₂H₅ 318 n-C₅H₁₁ n-C₄H₉ 319 n-C₅H₁₁ n-C₅H₁₁ 320 n-C₅H₁₁n-C₆H₁₃ 321 n-C₅H₁₁ n-C₇H₁₅ 322 n-C₆H₁₃ H 323 n-C₆H₁₃ CH₃ 324 n-C₆H₁₃C₂H₅ 325 n-C₆H₁₃ n-C₃H₇ 326 n-C₆H₁₃ n-C₄H₉ 327 n-C₆H₁₃ n-C₅H₁₁ 328n-C₆H₁₃ n-C₆H₁₃ 329 n-C₆H₁₃ n-C₇H₁₅ 330 n-C₇H₁₅ H 331 n-C₇H₁₅ CH₃ 332n-C₇H₁₅ C₂H₅ 333 n-C₇H₁₅ n-C₃H₇ 334 n-C₇H₁₅ n-C₄H₉ 335 n-C₇H₁₅ n-C₅H₁₁336 n-C₇H₁₅ n-C₆H₁₃ 337 n-C₇H₁₅ n-C₇H₁₅ 338 CH₃ H 339 CH₃ CH₃ 340 CH₃C₂H₅ 341 CH₃ n-C₃H₇ 342 CH₃ n-C₄H₉ 343 CH₃ n-C₅H₁₁ 344 CH₃ n-C₆H₁₃ 345CH₃ n-C₇H₁₅ 346 C₂H₅ H 347 C₂H₅ CH₃ 348 C₂H₅ C₂H₅ 349 C₂H₅ n-C₃H₇ 350C₂H₅ n-C₄H₉ 351 C₂H₅ n-C₅H₁₁ 352 C₂H₅ n-C₆H₁₃ 353 C₂H₅ n-C₇H₁₅ 354n-C₃H₇ H 355 n-C₃H₇ CH₃ 356 n-C₃H₇ C₂H₅ 357 n-C₃H₇ n-C₄H₉ 358 n-C₃H₇n-C₅H₁₁ 359 n-C₃H₇ n-C₆H₁₃ 360 n-C₃H₇ n-C₇H₁₅ 361 n-C₄H₉ H 362 n-C₄H₉CH₃ 363 n-C₄H₉ C₂H₅ 364 n-C₄H₉ n-C₃H₇ 365 n-C₄H₉ n-C₄H₉ 366 n-C₄H₉n-C₅H₁₁ 367 n-C₄H₉ n-C₆H₁₃ 368 n-C₄H₉ n-C₇H₁₅ 369 n-C₅H₁₁ H 370 n-C₅H₁₁CH₃ 371 n-C₅H₁₁ C₂H₅ 372 n-C₅H₁₁ n-C₃H₇ 373 n-C₅H₁₁ n-C₄H₉ 374 n-C₅H₁₁n-C₅H₁₁ 375 n-C₅H₁₁ n-C₆H₁₃ 376 n-C₅H₁₁ n-C₇H₁₅ 377 n-C₆H₁₃ H 378n-C₆H₁₃ CH₃ 379 n-C₆H₁₃ C₂H₅ 380 n-C₆H₁₃ n-C₃H₇ 381 n-C₆H₁₃ n-C₄H₉ 382n-C₆H₁₃ n-C₅H₁₁ 383 n-C₆H₁₃ n-C₆H₁₃ 384 n-C₆H₁₃ n-C₇H₁₅ 385 n-C₇H₁₅ H386 n-C₇H₁₅ CH₃ 387 n-C₇H₁₅ C₂H₅ 388 n-C₇H₁₅ n-C₃H₇ 389 n-C₇H₁₅ n-C₄H₉390 n-C₇H₁₅ n-C₅H₁₁ 391 n-C₇H₁₅ n-C₆H₁₃ 392 n-C₇H₁₅ n-C₇H₁₅ 393 CH₃ H394 CH₃ CH₃ 395 CH₃ C₂H₅ 396 CH₃ n-C₃H₇ 397 CH₃ n-C₄H₉ 398 CH₃ n-C₅H₁₁399 CH₃ n-C₆H₁₃ 400 CH₃ n-C₇H₁₅ 401 C₂H₅ H 402 C₂H₅ CH₃ 403 C₂H₅ C₂H₅404 C₂H₅ n-C₃H₇ 405 C₂H₅ n-C₄H₉ 406 C₂H₅ n-C₅H₁₁ 407 C₂H₅ n-C₆H₁₃ 408C₂H₅ n-C₇H₁₅ 409 n-C₃H₇ H 410 n-C₃H₇ CH₃ 411 n-C₃H₇ C₂H₅ 412 n-C₃H₇n-C₄H₉ 413 n-C₃H₇ n-C₅H₁₁ 414 n-C₃H₇ n-C₆H₁₃ 415 n-C₃H₇ n-C₇H₁₅ 416n-C₄H₉ H 417 n-C₄H₉ CH₃ 418 n-C₄H₉ C₂H₅ 419 n-C₄H₉ n-C₃H₇ 420 n-C₄H₉n-C₄H₉ 421 n-C₄H₉ n-C₅H₁₁ 422 n-C₄H₉ n-C₆H₁₃ 423 n-C₄H₉ n-C₇H₁₅ 424n-C₅H₁₁ H 425 n-C₅H₁₁ CH₃ 426 n-C₅H₁₁ C₂H₅ 427 n-C₅H₁₁ n-C₃H₇ 428n-C₅H₁₁ n-C₄H₉ 429 n-C₅H₁₁ n-C₅H₁₁ 430 n-C₅H₁₁ n-C₆H₁₃ 431 n-C₅H₁₁n-C₇H₁₅ 432 n-C₆H₁₃ H 433 n-C₆H₁₃ CH₃ 434 n-C₆H₁₃ C₂H₅ 435 n-C₆H₁₃n-C₃H₇ 436 n-C₆H₁₃ n-C₄H₉ 437 n-C₆H₁₃ n-C₅H₁₁ 438 n-C₆H₁₃ n-C₆H₁₃ 439n-C₆H₁₃ n-C₇H₁₅ 440 n-C₇H₁₅ H 441 n-C₇H₁₅ CH₃ 442 n-C₇H₁₅ C₂H₅ 443n-C₇H₁₅ n-C₃H₇ 444 n-C₇H₁₅ n-C₄H₉ 445 n-C₇H₁₅ n-C₅H₁₁ 446 n-C₇H₁₅n-C₆H₁₃ 447 n-C₇H₁₅ n-C₇H₁₅ 448 CH₃ H 449 CH₃ CH₃ 450 CH₃ C₂H₅ 451 CH₃n-C₃H₇ 452 CH₃ n-C₄H₉ 453 CH₃ n-C₅H₁₁ 454 CH₃ n-C₆H₁₃ 455 CH₃ n-C₇H₁₅456 C₂H₅ H 457 C₂H₅ CH₃ 458 C₂H₅ C₂H₅ 459 C₂H₅ n-C₃H₇ 460 C₂H₅ n-C₄H₉461 C₂H₅ n-C₅H₁₁ 462 C₂H₅ n-C₆H₁₃ 463 C₂H₅ n-C₇H₁₅ 464 n-C₃H₇ H 465n-C₃H₇ CH₃ 466 n-C₃H₇ C₂H₅ 467 n-C₃H₇ n-C₄H₉ 468 n-C₃H₇ n-C₅H₁₁ 469n-C₃H₇ n-C₆H₁₃ 470 n-C₃H₇ n-C₇H₁₅ 471 n-C₄H₉ H 472 n-C₄H₉ CH₃ 473 n-C₄H₉C₂H₅ 474 n-C₄H₉ n-C₃H₇ 475 n-C₄H₉ n-C₄H₉ 476 n-C₄H₉ n-C₅H₁₁ 477 n-C₄H₉n-C₆H₁₃ 478 n-C₄H₉ n-C₇H₁₅ 479 n-C₅H₁₁ H 480 n-C₅H₁₁ CH₃ 481 n-C₅H₁₁C₂H₅ 482 n-C₅H₁₁ n-C₃H₇ 483 n-C₅H₁₁ n-C₄H₉ 484 n-C₅H₁₁ n-C₅H₁₁ 485n-C₅H₁₁ n-C₆H₁₃ 486 n-C₅H₁₁ n-C₇H₁₅ 487 n-C₆H₁₃ H 488 n-C₆H₁₃ CH₃ 489n-C₆H₁₃ C₂H₅ 490 n-C₆H₁₃ n-C₃H₇ 491 n-C₆H₁₃ n-C₄H₉ 492 n-C₆H₁₃ n-C₅H₁₁493 n-C₆H₁₃ n-C₆H₁₃ 494 n-C₆H₁₃ n-C₇H₁₅ 495 n-C₇H₁₅ H 496 n-C₇H₁₅ CH₃497 n-C₇H₁₅ C₂H₅ 498 n-C₇H₁₅ n-C₃H₇ 499 n-C₇H₁₅ n-C₄H₉ 500 n-C₇H₁₅n-C₅H₁₁ 501 n-C₇H₁₅ n-C₆H₁₃ 502 n-C₇H₁₅ n-C₇H₁₅ 503 CH₃ H 504 CH₃ CH₃505 CH₃ C₂H₅ 506 CH₃ n-C₃H₇ 507 CH₃ n-C₄H₉ 508 CH₃ n-C₅H₁₁ 509 CH₃n-C₆H₁₃ 510 CH₃ n-C₇H₁₅ 511 C₂H₅ H 512 C₂H₅ CH₃ 513 C₂H₅ C₂H₅ 514 C₂H₅n-C₃H₇ 515 C₂H₅ n-C₄H₉ 516 C₂H₅ n-C₅H₁₁ 517 C₂H₅ n-C₆H₁₃ 518 C₂H₅n-C₇H₁₅ 519 n-C₃H₇ H 520 n-C₃H₇ CH₃ 521 n-C₃H₇ C₂H₅ 522 n-C₃H₇ n-C₄H₉523 n-C₃H₇ n-C₅H₁₁ 524 n-C₃H₇ n-C₆H₁₃ 525 n-C₃H₇ n-C₇H₁₅ 526 n-C₄H₉ H527 n-C₄H₉ CH₃ 528 n-C₄H₉ C₂H₅ 529 n-C₄H₉ n-C₃H₇ 530 n-C₄H₉ n-C₄H₉ 531n-C₄H₉ n-C₅H₁₁ 532 n-C₄H₉ n-C₆H₁₃ 533 n-C₄H₉ n-C₇H₁₅ 534 n-C₅H₁₁ H 535n-C₅H₁₁ CH₃ 536 n-C₅H₁₁ C₂H₅ 537 n-C₅H₁₁ n-C₃H₇ 538 n-C₅H₁₁ n-C₄H₉ 539n-C₅H₁₁ n-C₅H₁₁ 540 n-C₅H₁₁ n-C₆H₁₃ 541 n-C₅H₁₁ n-C₇H₁₅ 542 n-C₆H₁₃ H543 n-C₆H₁₃ CH₃ 544 n-C₆H₁₃ C₂H₅ 545 n-C₆H₁₃ n-C₃H₇ 546 n-C₆H₁₃ n-C₄H₉547 n-C₆H₁₃ n-C₅H₁₁ 548 n-C₆H₁₃ n-C₆H₁₃ 549 n-C₆H₁₃ n-C₇H₁₅ 550 n-C₇H₁₅H 551 n-C₇H₁₅ CH₃ 552 n-C₇H₁₅ C₂H₅ 553 n-C₇H₁₅ n-C₃H₇ 554 n-C₇H₁₅ n-C₄H₉555 n-C₇H₁₅ n-C₅H₁₁ 556 n-C₇H₁₅ n-C₆H₁₃ 557 n-C₇H₁₅ n-C₇H₁₅ 558 CH₃ H559 CH₃ CH₃ 560 CH₃ C₂H₅ 561 CH₃ n-C₃H₇ 562 CH₃ n-C₄H₉ 563 CH₃ n-C₅H₁₁564 CH₃ n-C₆H₁₃ 565 CH₃ n-C₇H₁₅ 566 C₂H₅ H 567 C₂H₅ CH₃ 568 C₂H₅ C₂H₅569 C₂H₅ n-C₃H₇ 570 C₂H₅ n-C₄H₉ 571 C₂H₅ n-C₅H₁₁ 572 C₂H₅ n-C₆H₁₃ 573C₂H₅ n-C₇H₁₅ 574 n-C₃H₇ H 575 n-C₃H₇ CH₃ 576 n-C₃H₇ C₂H₅ 577 n-C₃H₇n-C₄H₉ 578 n-C₃H₇ n-C₅H₁₁ 579 n-C₃H₇ n-C₆H₁₃ 580 n-C₃H₇ n-C₇H₁₅ 581n-C₄H₉ H 582 n-C₄H₉ CH₃ 583 n-C₄H₉ C₂H₅ 584 n-C₄H₉ n-C₃H₇ 585 n-C₄H₉n-C₄H₉ 586 n-C₄H₉ n-C₅H₁₁ 587 n-C₄H₉ n-C₆H₁₃ 588 n-C₄H₉ n-C₇H₁₅ 589n-C₅H₁₁ H 590 n-C₅H₁₁ CH₃ 591 n-C₅H₁₁ C₂H₅ 592 n-C₅H₁₁ n-C₃H₇ 593n-C₅H₁₁ n-C₄H₉ 594 n-C₅H₁₁ n-C₅H₁₁ 595 n-C₅H₁₁ n-C₆H₁₃ 596 n-C₅H₁₁n-C₇H₁₅ 597 n-C₆H₁₃ H 598 n-C₆H₁₃ CH₃ 599 n-C₆H₁₃ C₂H₅ 600 n-C₆H₁₃n-C₃H₇ 601 n-C₆H₁₃ n-C₄H₉ 602 n-C₆H₁₃ n-C₅H₁₁ 603 n-C₆H₁₃ n-C₆H₁₃ 604n-C₆H₁₃ n-C₇H₁₅ 605 n-C₇H₁₅ H 606 n-C₇H₁₅ CH₃ 607 n-C₇H₁₅ C₂H₅ 608n-C₇H₁₅ n-C₃H₇ 609 n-C₇H₁₅ n-C₄H₉ 610 n-C₇H₁₅ n-C₅H₁₁ 611 n-C₇H₁₅n-C₆H₁₃ 612 n-C₇H₁₅ n-C₇H₁₅ 613 CH₃ H 614 CH₃ CH₃ 615 CH₃ C₂H₅ 616 CH₃n-C₃H₇ 617 CH₃ n-C₄H₉ 618 CH₃ n-C₅H₁₁ 619 CH₃ n-C₆H₁₃ 620 CH₃ n-C₇H₁₅621 C₂H₅ H 622 C₂H₅ CH₃ 623 C₂H₅ C₂H₅ 624 C₂H₅ n-C₃H₇ 625 C₂H₅ n-C₄H₉626 C₂H₅ n-C₅H₁₁ 627 C₂H₅ n-C₆H₁₃ 628 C₂H₅ n-C₇H₁₅ 629 n-C₃H₇ H 630n-C₃H₇ CH₃ 631 n-C₃H₇ C₂H₅ 632 n-C₃H₇ n-C₄H₉ 633 n-C₃H₇ n-C₅H₁₁ 634n-C₃H₇ n-C₆H₁₃ 635 n-C₃H₇ n-C₇H₁₅ 636 n-C₄H₉ H 637 n-C₄H₉ CH₃ 638 n-C₄H₉C₂H₅ 639 n-C₄H₉ n-C₃H₇ 640 n-C₄H₉ n-C₄H₉ 641 n-C₄H₉ n-C₅H₁₁ 642 n-C₄H₉n-C₆H₁₃ 643 n-C₄H₉ n-C₇H₁₅ 644 n-C₅H₁₁ H 645 n-C₅H₁₁ CH₃ 646 n-C₅H₁₁C₂H₅ 647 n-C₅H₁₁ n-C₃H₇ 648 n-C₅H₁₁ n-C₄H₉ 649 n-C₅H₁₁ n-C₅H₁₁ 650n-C₅H₁₁ n-C₆H₁₃ 651 n-C₅H₁₁ n-C₇H₁₅ 652 n-C₆H₁₃ H 653 n-C₆H₁₃ CH₃ 654n-C₆H₁₃ C₂H₅ 655 n-C₆H₁₃ n-C₃H₇ 656 n-C₆H₁₃ n-C₄H₉ 657 n-C₆H₁₃ n-C₅H₁₁658 n-C₆H₁₃ n-C₆H₁₃ 659 n-C₆H₁₃ n-C₇H₁₅ 660 n-C₇H₁₅ H 661 n-C₇H₁₅ CH₃662 n-C₇H₁₅ C₂H₅ 663 n-C₇H₁₅ n-C₃H₇ 664 n-C₇H₁₅ n-C₄H₉ 665 n-C₇H₁₅n-C₅H₁₁ 666 n-C₇H₁₅ n-C₆H₁₃ 667 n-C₇H₁₅ n-C₇H₁₅

Analogously to Example 2: Examples 668 to 715:

Analogously to Example 2: Examples 716 to 767:

Analogously to Example 2: Examples 768 to 815:

Analogously to Example 2: Examples 816 to 863:

Analogously to Example 2: Examples 864 to 911:

Analogously to Example 2: Examples 912 to 959:

TABLE 3

Ex. R¹ R² 668 CH₃ CH₃ 669 CH₃ C₂H₅ 670 CH₃ n-C₃H₇ 671 CH₃ n-C₄H₉ 672 CH₃n-C₅H₁₁ 673 CH₃ n-C₆H₁₃ 674 CH₃ n-C₇H₁₅ 675 C₂H₅ CH₃ 676 C₂H₅ C₂H₅ 677C₂H₅ n-C₃H₇ 678 C₂H₅ n-C₄H₉ 679 C₂H₅ n-C₅H₁₁ 680 C₂H₅ n-C₆H₁₃ 681 C₂H₅n-C₇H₁₅ 682 n-C₃H₇ CH₃ 683 n-C₃H₇ C₂H₅ 684 n-C₃H₇ n-C₄H₉ 685 n-C₃H₇n-C₅H₁₁ 686 n-C₃H₇ n-C₆H₁₃ 687 n-C₃H₇ n-C₇H₁₅ 688 n-C₄H₉ CH₃ 689 n-C₄H₉C₂H₅ 690 n-C₄H₉ n-C₃H₇ 691 n-C₄H₉ n-C₄H₉ 692 n-C₄H₉ n-C₅H₁₁ 693 n-C₄H₉n-C₆H₁₃ 694 n-C₄H₉ n-C₇H₁₅ 695 n-C₅H₁₁ CH₃ 696 n-C₅H₁₁ C₂H₅ 697 n-C₅H₁₁n-C₃H₇ 698 n-C₅H₁₁ n-C₄H₉ 699 n-C₅H₁₁ n-C₅H₁₁ 700 n-C₅H₁₁ n-C₆H₁₃ 701n-C₅H₁₁ n-C₇H₁₅ 702 n-C₆H₁₃ CH₃ 703 n-C₆H₁₃ C₂H₅ 704 n-C₆H₁₃ n-C₃H₇ 705n-C₆H₁₃ n-C₄H₉ 706 n-C₆H₁₃ n-C₅H₁₁ 707 n-C₆H₁₃ n-C₆H₁₃ 708 n-C₆H₁₃n-C₇H₁₅ 709 n-C₇H₁₅ CH₃ 710 n-C₇H₁₅ C₂H₅ 711 n-C₇H₁₅ n-C₃H₇ 712 n-C₇H₁₅n-C₄H₉ 713 n-C₇H₁₅ n-C₅H₁₁ 714 n-C₇H₁₅ n-C₆H₁₃ 715 n-C₇H₁₅ n-C₇H₁₅ 716CH₃ CH₃ 717 CH₃ C₂H₅ 718 CH₃ n-C₃H₇ 719 CH₃ n-C₄H₉ 720 CH₃ n-C₅H₁₁ 721CH₃ n-C₆H₁₃ 722 CH₃ n-C₇H₁₅ 723 C₂H₅ CH₃ 724 C₂H₅ C₂H₅ 725 C₂H₅ n-C₃H₇726 C₂H₅ n-C₄H₉ 727 C₂H₅ n-C₅H₁₁ 728 C₂H₅ n-C₆H₁₃ 729 C₂H₅ n-C₇H₁₅ 730n-C₃H₇ CH₃ 731 n-C₃H₇ C₂H₅ 732 n-C₃H₇ n-C₄H₉ 733 n-C₃H₇ n-C₅H₁₁ 734n-C₄H₇ n-C₆H₁₃ 735 n-C₃H₇ n-C₇H₁₅ 736 n-C₄H₉ CH₃ 737 n-C₄H₉ C₂H₅ 738n-C₄H₉ n-C₃H₇ 739 n-C₄H₉ n-C₄H₉ 740 n-C₄H₉ n-C₅H₁₁ 741 n-C₄H₉ n-C₆H₁₃742 n-C₄H₉ n-C₇H₁₅ 743 n-C₅H₁₁ CH₃ 744 n-C₅H₁₁ C₂H₅ 745 n-C₅H₁₁ n-C₃H₇746 n-C₅H₁₁ n-C₄H₉ 747 n-C₅H₁₁ n-C₅H₁₁ 748 n-C₅H₁₁ n-C₆H₁₃ 749 n-C₅H₁₁n-C₇H₁₅ 750 n-C₆H₁₃ CH₃ 751 n-C₆H₁₃ C₂H₅ 752 n-C₆H₁₃ n-C₃H₇ 753 n-C₆H₁₃n-C₄H₉ 754 n-C₆H₁₃ n-C₅H₁₁ 755 n-C₆H₁₃ n-C₆H₁₃ 756 n-C₆H₁₃ n-C₇H₁₅ 757n-C₇H₁₅ CH₃ 758 n-C₇H₁₅ C₂H₅ 759 n-C₇H₁₅ n-C₃H₇ 760 n-C₇H₁₅ n-C₄H₉ 761n-C₇H₁₅ n-C₅H₁₁ 762 n-C₇H₁₅ n-C₆H₁₃ 763 n-C₇H₁₅ n-C₇H₁₅ 768 CH₃ CH₃ 769CH₃ C₂H₅ 770 CH₃ n-C₃H₇ 771 CH₃ n-C₄H₉ 772 CH₃ n-C₅H₁₁ 773 CH₃ n-C₆H₁₃774 CH₃ n-C₇H₁₅ 775 C₂H₅ CH₃ 776 C₂H₅ C₂H₅ 777 C₂H₅ n-C₃H₇ 778 C₂H₅n-C₄H₉ 779 C₂H₅ n-C₅H₁₁ 780 C₂H₅ n-C₆H₁₃ 781 C₂H₅ n-C₇H₁₅ 782 n-C₃H₇ CH₃783 n-C₃H₇ C₂H₅ 784 n-C₃H₇ n-C₄H₉ 785 n-C₃H₇ n-C₅H₁₁ 786 n-C₃H₇ n-C₆H₁₃787 n-C₃H₇ n-C₇H₁₅ 788 n-C₄H₉ CH₃ 789 n-C₄H₉ C₂H₅ 790 n-C₄H₉ n-C₃H₇ 791n-C₄H₉ n-C₄H₉ 792 n-C₄H₉ n-C₅H₁₁ 793 n-C₄H₉ n-C₆H₁₃ 794 n-C₄H₉ n-C₇H₁₅795 n-C₅H₁₁ CH₃ 796 n-C₅H₁₁ C₂H₅ 797 n-C₅H₁₁ n-C₃H₇ 798 n-C₅H₁₁ n-C₄H₉799 n-C₅H₁₁ n-C₅H₁₁ 800 n-C₅H₁₁ n-C₆H₁₃ 801 n-C₅H₁₁ n-C₇H₁₅ 802 n-C₆H₁₃CH₃ 803 n-C₆H₁₃ C₂H₅ 804 n-C₆H₁₃ n-C₃H₇ 805 n-C₆H₁₃ n-C₄H₉ 806 n-C₆H₁₃n-C₅H₁₁ 807 n-C₆H₁₃ n-C₆H₁₃ 808 n-C₆H₁₃ n-C₇H₁₅ 809 n-C₇H₁₅ CH₃ 810n-C₇H₁₅ C₂H₅ 811 n-C₇H₁₅ n-C₃H₇ 812 n-C₇H₁₅ n-C₄H₉ 813 n-C₇H₁₅ n-C₅H₁₁814 n-C₇H₁₅ n-C₆H₁₃ 815 n-C₇H₁₅ n-C₇H₁₅ 816 CH₃ CH₃ 817 CH₃ C₂H₅ 818 CH₃n-C₃H₇ 819 CH₃ n-C₄H₉ 820 CH₃ n-C₅H₁₁ 821 CH₃ n-C₆H₁₃ 822 CH₃ n-C₇H₁₅823 C₂H₅ CH₃ 824 C₂H₅ C₂H₅ 825 C₂H₅ n-C₃H₇ 826 C₂H₅ n-C₄H₉ 827 C₂H₅n-C₅H₁₁ 828 C₂H₅ n-C₆H₁₃ 829 C₂H₄ n-C₇H₁₅ 830 n-C₃H₇ CH₃ 831 n-C₃H₇ C₂H₅832 n-C₃H₇ n-C₄H₉ 833 n-C₃H₇ n-C₅H₁₁ 834 n-C₃H₇ n-C₆H₁₃ 835 n-C₃H₇n-C₇H₁₅ 836 n-C₄H₉ CH₃ 837 n-C₄H₉ C₂H₅ 838 n-C₄H₉ n-C₃H₇ 839 n-C₄H₉n-C₄H₉ 840 n-C₄H₉ n-C₅H₁₁ 841 n-C₄H₉ n-C₆H₁₃ 842 n-C₄H₉ n-C₇H₁₅ 843n-C₅H₁₁ CH₃ 844 n-C₅H₁₁ C₂H₅ 845 n-C₅H₁₁ n-C₃H₇ 846 n-C₅H₁₁ n-C₄H₉ 847n-C₅H₁₁ n-C₅H₁₁ 848 n-C₅H₁₁ n-C₆H₁₃ 849 n-C₅H₁₁ n-C₇H₁₅ 850 n-C₆H₁₃ CH₃851 n-C₆H₁₃ C₂H₅ 852 n-C₆H₁₃ n-C₃H₇ 853 n-C₆H₁₃ n-C₄H₉ 854 n-C₆H₁₃n-C₅H₁₁ 855 n-C₆H₁₃ n-C₆H₁₃ 856 n-C₆H₁₃ n-C₇H₁₅ 857 n-C₇H₁₅ CH₃ 858n-C₇H₁₅ C₂H₅ 859 n-C₇H₁₅ n-C₃H₇ 860 n-C₇H₁₅ n-C₄H₉ 861 n-C₇H₁₅ n-C₅H₁₁862 n-C₇H₁₅ n-C₆H₁₃ 863 n-C₇H₁₅ n-C₇H₁₅ 864 CH₃ CH₃ 865 CH₃ C₂H₅ 866 CH₃n-C₃H₇ 867 CH₃ n-C₄H₉ 868 CH₃ n-C₅H₁₁ 869 CH₃ n-C₆H₁₃ 870 CH₃ n-C₇H₁₅871 C₂H₅ CH₃ 872 C₂H₅ C₂H₅ 873 C₂H₅ n-C₃H₇ 874 C₂H₅ n-C₄H₉ 875 C₂H₅n-C₅H₁₁ 876 C₂H₅ n-C₆H₁₃ 877 C₂H₅ n-C₇H₁₅ 878 n-C₃H₇ CH₃ 879 n-C₃H₇ C₂H₅880 n-C₃H₇ n-C₄H₉ 881 n-C₃H₇ n-C₅H₁₁ 882 n-C₃H₇ n-C₆H₁₃ 883 n-C₃H₇n-C₇H₁₅ 884 n-C₄H₉ CH₃ 885 n-C₄H₉ C₂H₅ 886 n-C₄H₉ n-C₃H₇ 887 n-C₄H₉n-C₄H₉ 888 n-C₄H₉ n-C₅H₁₁ 889 n-C₄H₉ n-C₆H₁₃ 890 n-C₄H₉ n-C₇H₁₅ 891n-C₅H₁₁ CH₃ 892 n-C₅H₁₁ C₂H₅ 893 n-C₅H₁₁ n-C₃H₇ 894 n-C₅H₁₁ n-C₄H₉ 895n-C₅H₁₁ n-C₅H₁₁ 896 n-C₅H₁₁ n-C₆H₁₃ 897 n-C₅H₁₁ n-C₇H₁₅ 898 n-C₆H₁₃ CH₃899 n-C₆H₁₃ C₂H₅ 900 n-C₆H₁₃ n-C₃H₇ 901 n-C₆H₁₃ n-C₄H₉ 902 n-C₆H₁₃n-C₅H₁₁ 903 n-C₆H₁₃ n-C₆H₁₃ 904 n-C₆H₁₃ n-C₇H₁₅ 905 n-C₇H₁₅ CH₃ 906n-C₇H₁₅ C₂H₅ 907 n-C₇H₁₅ n-C₃H₇ 908 n-C₇H₁₅ n-C₄H₉ 909 n-C₇H₁₅ n-C₅H₁₁910 n-C₇H₁₅ n-C₆H₁₃ 911 n-C₇H₁₅ n-C₇H₁₅ 912 CH₃ CH₃ 913 CH₃ C₂H₅ 914 CH₃n-C₃H₇ 915 CH₃ n-C₄H₉ 916 CH₃ n-C₅H₁₁ 917 CH₃ n-C₆H₁₃ 918 CH₃ n-C₇H₁₅919 C₂H₅ CH₃ 920 C₂H₅ C₂H₅ 921 C₂H₅ n-C₃H₇ 922 C₂H₅ n-C₄H₉ 923 C₂H₅n-C₅H₁₁ 924 C₂H₅ n-C₆H₁₃ 925 C₂H₅ n-C₇H₁₅ 926 n-C₃H₇ CH₃ 927 n-C₃H₇ C₂H₅928 n-C₃H₇ n-C₄H₉ 929 n-C₃H₇ n-C₅H₁₁ 930 n-C₃H₇ n-C₆H₁₃ 931 n-C₃H₇n-C₇H₁₅ 932 n-C₄H₉ CH₃ 933 n-C₄H₉ C₂H₅ 934 n-C₄H₉ n-C₃H₇ 935 n-C₄H₉n-C₄H₉ 936 n-C₄H₉ n-C₅H₁₁ 937 n-C₄H₉ n-C₆H₁₃ 938 n-C₄H₉ n-C₇H₁₅ 939n-C₅H₁₁ CH₃ 940 n-C₅H₁₁ C₂H₅ 941 n-C₅H₁₁ n-C₃H₇ 942 n-C₅H₁₁ n-C₄H₉ 943n-C₅H₁₁ n-C₅H₁₁ 944 n-C₅H₁₁ n-C₆H₁₃ 945 n-C₅H₁₁ n-C₇H₁₅ 946 n-C₆H₁₃ CH₃947 n-C₆H₁₃ C₂H₅ 948 n-C₆H₁₃ n-C₃H₇ 949 n-C₆H₁₃ n-C₄H₉ 950 n-C₆H₁₃n-C₅H₁₁ 951 n-C₆H₁₃ n-C₆H₁₃ 952 n-C₆H₁₃ n-C₇H₁₅ 953 n-C₇H₁₅ CH₃ 954n-C₇H₁₅ C₂H₅ 955 n-C₇H₁₅ n-C₃H₇ 956 n-C₇H₁₅ n-C₄H₉ 957 n-C₇H₁₅ n-C₅H₁₁958 n-C₇H₁₅ n-C₆H₁₃ 959 n-C₇H₁₅ n-C₇H₁₅

Analogously to Example 6: Examples 960 to 1014:

Analogously to Example 6: Examples 1015 to 1069:

Analogously to Example 7: Examples 1070 to 1124:

Analogously to Example 7: Examples 1125 to 1179:

TABLE 4

Ex. R¹ R² 960 CH₃ H 961 CH₃ CH₃ 962 CH₃ C₂H₅ 963 CH₃ n-C₃H₇ 964 CH₃n-C₄H₉ 965 CH₃ n-C₅H₁₁ 966 CH₃ n-C₆H₁₃ 967 CH₃ n-C₇H₁₅ 968 C₂H₅ H 969C₂H₅ CH₃ 970 C₂H₅ C₂H₅ 971 C₂H₅ n-C₃H₇ 972 C₂H₅ n-C₄H₉ 973 C₂H₅ n-C₅H₁₁974 C₂H₅ n-C₆H₁₃ 975 C₂H₅ n-C₇H₁₅ 976 n-C₃H₇ H 977 n-C₃H₇ CH₃ 978 n-C₃H₇C₂H₅ 979 n-C₃H₇ n-C₄H₉ 980 n-C₃H₇ n-C₅H₁₁ 981 n-C₃H₇ n-C₆H₁₃ 982 n-C₃H₇n-C₇H₁₅ 983 n-C₄H₉ H 984 n-C₄H₉ CH₃ 985 n-C₄H₉ C₂H₅ 986 n-C₄H₉ n-C₃H₇987 n-C₄H₉ n-C₄H₉ 988 n-C₄H₉ n-C₅H₁₁ 989 n-C₄H₉ n-C₆H₁₃ 990 n-C₄H₉n-C₇H₁₅ 991 n-C₅H₁₁ H 992 n-C₅H₁₁ CH₃ 993 n-C₅H₁₁ C₂H₅ 994 n-C₅H₁₁n-C₃H₇ 995 n-C₅H₁₁ n-C₄H₉ 996 n-C₅H₁₁ n-C₅H₁₁ 997 n-C₅H₁₁ n-C₆H₁₃ 998n-C₅H₁₁ n-C₇H₁₅ 999 n-C₆H₁₃ H 1000 n-C₆H₁₃ CH₃ 1001 n-C₆H₁₃ C₂H₅ 1002n-C₆H₁₃ n-C₃H₇ 1003 n-C₆H₁₃ n-C₄H₉ 1004 n-C₆H₁₃ n-C₅H₁₁ 1005 n-C₆H₁₃n-C₆H₁₃ 1006 n-C₆H₁₃ n-C₇H₁₅ 1007 n-C₇H₁₅ H 1008 n-C₇H₁₅ CH₃ 1009n-C₇H₁₅ C₂H₅ 1010 n-C₇H₁₅ n-C₃H₇ 1011 n-C₇H₁₅ n-C₄H₉ 1012 n-C₇H₁₅n-C₅H₁₁ 1013 n-C₇H₁₅ n-C₆H₁₃ 1014 n-C₇H₁₅ n-C₇H₁₅ 1015 CH₃ H 1016 CH₃CH₃ 1017 CH₃ C₂H₅ 1018 CH₃ n-C₃H₇ 1019 CH₃ n-C₄H₉ 1020 CH₃ n-C₅H₁₁ 1021CH₃ n-C₆H₁₃ 1022 CH₃ n-C₇H₁₅ 1023 C₂H₅ H 1024 C₂H₅ CH₃ 1025 C₂H₅ C₂H₅1026 C₂H₅ n-C₃H₇ 1027 C₂H₅ n-C₄H₉ 1028 C₂H₅ n-C₅H₁₁ 1029 C₂H₅ n-C₆H₁₃1030 C₂H₅ n-C₇H₁₅ 1031 n-C₃H₇ H 1032 n-C₃H₇ CH₃ 1033 n-C₃H₇ C₂H₅ 1034n-C₃H₇ n-C₄H₉ 1035 n-C₃H₇ n-C₅H₁₁ 1036 n-C₃H₇ n-C₆H₁₃ 1037 n-C₃H₇n-C₇H₁₅ 1038 n-C₄H₉ H 1039 n-C₄H₉ CH₃ 1040 n-C₄H₉ C₂H₅ 1041 n-C₄H₉n-C₃H₇ 1042 n-C₄H₉ n-C₄H₉ 1043 n-C₄H₉ n-C₅H₁₁ 1044 n-C₄H₉ n-C₆H₁₃ 1045n-C₄H₉ n-C₇H₁₅ 1046 n-C₅H₁₁ H 1047 n-C₅H₁₁ CH₃ 1048 n-C₅H₁₁ C₂H₅ 1049n-C₅H₁₁ n-C₃H₇ 1050 n-C₅H₁₁ n-C₄H₉ 1051 n-C₅H₁₁ n-C₅H₁₁ 1052 n-C₅H₁₁n-C₆H₁₃ 1053 n-C₅H₁₁ n-C₇H₁₅ 1054 n-C₆H₁₃ H 1055 n-C₆H₁₃ CH₃ 1056n-C₆H₁₃ C₂H₅ 1057 n-C₆H₁₃ n-C₃H₇ 1058 n-C₆H₁₃ n-C₄H₉ 1059 n-C₆H₁₃n-C₅H₁₁ 1060 n-C₆H₁₃ n-C₆H₁₃ 1061 n-C₆H₁₃ n-C₇H₁₅ 1062 n-C₇H₁₅ H 1063n-C₇H₁₅ CH₃ 1064 n-C₇H₁₅ C₂H₅ 1065 n-C₇H₁₅ n-C₃H₇ 1066 n-C₇H₁₅ n-C₄H₉1067 n-C₇H₁₅ n-C₅H₁₁ 1068 n-C₇H₁₅ n-C₆H₁₃ 1069 n-C₇H₁₅ n-C₇H₁₅ 1070 CH₃H 1071 CH₃ CH₃ 1072 CH₃ C₂H₅ 1073 CH₃ n-C₃H₇ 1074 CH₃ n-C₄H₉ 1075 CH₃n-C₅H₁₁ 1076 CH₃ n-C₆H₁₃ 1077 CH₃ n-C₇H₁₅ 1078 C₂H₅ H 1079 C₂H₅ CH₃ 1080C₂H₅ C₂H₅ 1081 C₂H₅ n-C₃H₇ 1082 C₂H₅ n-C₄H₉ 1083 C₂H₅ n-C₅H₁₁ 1084 C₂H₅n-C₆H₁₃ 1085 C₂H₅ n-C₇H₁₅ 1086 n-C₃H₇ H 1087 n-C₃H₇ CH₃ 1088 n-C₃H₇ C₂H₅1089 n-C₃H₇ n-C₄H₉ 1090 n-C₃H₇ n-C₅H₁₁ 1091 n-C₃H₇ n-C₆H₁₃ 1092 n-C₃H₇n-C₇H₁₅ 1093 n-C₄H₉ H 1094 n-C₄H₉ CH₃ 1095 n-C₄H₉ C₂H₅ 1096 n-C₄H₉n-C₃H₇ 1097 n-C₄H₉ n-C₄H₉ 1098 n-C₄H₉ n-C₅H₁₁ 1099 n-C₄H₉ n-C₆H₁₃ 1100n-C₄H₉ n-C₇H₁₅ 1101 n-C₅H₁₁ H 1102 n-C₅H₁₁ CH₃ 1103 n-C₅H₁₁ C₂H₅ 1104n-C₅H₁₁ n-C₃H₇ 1105 n-C₅H₁₁ n-C₄H₉ 1106 n-C₅H₁₁ n-C₅H₁₁ 1107 n-C₅H₁₁n-C₆H₁₃ 1108 n-C₅H₁₁ n-C₇H₁₅ 1109 n-C₆H₁₃ H 1110 n-C₆H₁₃ CH₃ 1111n-C₆H₁₃ C₂H₅ 1112 n-C₆H₁₃ n-C₃H₇ 1113 n-C₆H₁₃ n-C₄H₉ 1114 n-C₆H₁₃n-C₅H₁₁ 1115 n-C₆H₁₃ n-C₆H₁₃ 1116 n-C₆H₁₃ n-C₇H₁₅ 1117 n-C₇H₁₅ H 1118n-C₇H₁₅ CH₃ 1119 n-C₇H₁₅ C₂H₅ 1120 n-C₇H₁₅ n-C₃H₇ 1121 n-C₇H₁₅ n-C₄H₉1122 n-C₇H₁₅ n-C₅H₁₁ 1123 n-C₇H₁₅ n-C₆H₁₃ 1124 n-C₇H₁₅ n-C₇H₁₅ 1125 CH₃H 1126 CH₃ CH₃ 1127 CH₃ C₂H₅ 1128 CH₃ n-C₃H₇ 1129 CH₃ n-C₄H₉ 1130 CH₃n-C₅H₁₁ 1131 CH₃ n-C₆H₁₃ 1132 CH₃ n-C₇H₁₅ 1133 C₂H₅ H 1134 C₂H₅ CH₃ 1135C₂H₅ C₂H₅ 1136 C₂H₅ n-C₃H₇ 1137 C₂H₅ n-C₄H₉ 1138 C₂H₅ n-C₅H₁₁ 1139 C₂H₅n-C₆H₁₃ 1140 C₂H₅ n-C₇H₁₅ 1141 n-C₃H₇ H 1142 n-C₃H₇ CH₃ 1143 n-C₃H₇ C₂H₅1144 n-C₃H₇ n-C₄H₉ 1145 n-C₃H₇ n-C₅H₁₁ 1146 n-C₃H₇ n-C₆H₁₃ 1147 n-C₃H₇n-C₇H₁₅ 1148 n-C₄H₉ H 1149 n-C₄H₉ CH₃ 1150 n-C₄H₉ C₂H₅ 1151 n-C₄H₉n-C₃H₇ 1152 n-C₄H₉ n-C₄H₉ 1153 n-C₄H₉ n-C₅H₁₁ 1154 n-C₄H₉ n-C₆H₁₃ 1155n-C₄H₉ n-C₇H₁₅ 1156 n-C₅H₁₁ H 1157 n-C₅H₁₁ CH₃ 1158 n-C₅H₁₁ C₂H₅ 1159n-C₅H₁₁ n-C₃H₇ 1160 n-C₅H₁₁ n-C₄H₉ 1161 n-C₅H₁₁ n-C₅H₁₁ 1162 n-C₅H₁₁n-C₆H₁₃ 1163 n-C₅H₁₁ n-C₇H₁₅ 1164 n-C₆H₁₃ H 1165 n-C₆H₁₃ CH₃ 1166n-C₆H₁₃ C₂H₅ 1167 n-C₆H₁₃ n-C₃H₇ 1168 n-C₆H₁₃ n-C₄H₉ 1169 n-C₆H₁₃n-C₅H₁₁ 1170 n-C₆H₁₃ n-C₆H₁₃ 1171 n-C₆H₁₃ n-C₇H₁₅ 1172 n-C₇H₁₅ H 1173n-C₇H₁₅ CH₃ 1174 n-C₇H₁₅ C₂H₅ 1175 n-C₇H₁₅ n-C₃H₇ 1176 n-C₇H₁₅ n-C₄H₉1177 n-C₇H₁₅ n-C₅H₁₁ 1178 n-C₇H₁₅ n-C₆H₁₃ 1179 n-C₇H₁₅ n-C₇H₁₅

Values for individual compounds from all of Tables 1-4:

TABLE 5 Example Phase No. Δε Δn γ1 sequence 34 −5.1 0.088 132 C 114 I 36−5.0 0.090 171 C 116 I 99 −1.4 0.060 130 C 97 I 141 −5.4 0.098 102 C 120I 142 −5.4 0.094 149 C 124 I 144 −4.8 0.100 164 C 125 I 204 −1.9 0.06259 C 78 I

The entire disclosure[s] of all applications, patents and publications,cited herein and of corresponding DE 10 2006 019 045.9, filed Apr. 25,2006, are incorporated by reference herein.

The preceding examples can be repeated with similar success bysubstituting the generically or specifically described reactants and/oroperating conditions of this invention for those used in the precedingexamples.

From the foregoing description, one skilled in the art can easilyascertain the essential characteristics of this invention and, withoutdeparting from the spirit and scope thereof, can make various changesand modifications of the invention to adapt it to various usages andconditions.

1. A compound of formula I:

in which m and n each, independently of one another, are 0, 1 or 2, X¹,X² and X³ each, independently of one another, denote H, halogen, CN orCF₃, A¹ and A² each, independently of one another, denote 1,4-phenylene,in which ═CH— may be replaced once or twice by ═N— and which may beunsubstituted or mono-to tetrasubstituted, independently of one another,by —CN, —F, —Cl, —Br, —I, unsubstituted or mono- or polyfluorine- and/or-chlorine-substituted C₁-C₆-alkanyl, unsubstituted or mono- orpolyfluorine- and/or -chlorine-substituted C₁-C₆-alkoxy,1,4-cyclohexylene, 1,4-cyclohexenylene or 1,4-cyclohexadienylene, inwhich —CH₂— may be replaced once or twice, independently of one another,by —O— or —S— in such a way that heteroatoms are not linked directly,and which may be unsubstituted or mono- or poly-substituted by —F and/or—Cl, bicyclo[1.1.1]pentane-1,3-diyl, bicyclo[2.2.2]octane-1,4-diyl,spiro[3.3]heptane-2,6-diyl, tetrahydropyran-2,5-diyl or1,3-dioxane-2,5-diyl; Z¹ and Z² each, independently of one another,denote a single bond, —CF₂O—, —OCF₂—, —CH₂CH₂—, —CF₂CF₂—, —CF₂CH₂—,—CH₂CF₂—, —CHF—CHF—, —(CO)O—, —O(CO)—, —CH₂O—, —OCH₂—, —CF═CH—, —CH═CF—,—CF═CF—, —CH═CH— or —C≡C—; R¹ and R², independently of one another,denote hydrogen, an alkanyl, alkoxy, alkenyl or alkynyl radical havingup to 15 C atoms, which is unsubstituted, monosubstituted by —CN or —CF₃or mono- or polysubstituted by —F, —Cl, —Br and/or —I, in which one ormore CH₂ groups are optionally each, independently of one another,replaced by —O—, —S—, —SO₂—, —CO—, —(CO)O—, —O(CO)— or —O—CO—O— in sucha way that heteroatoms are not linked directly, —F, —Cl, —Br, —I, —CN,—SCN, —NCS or —SF₅; where A¹, A², Z¹, Z² may each have identical ordifferent meanings if m or n respectively is greater than 1, and wherein the case where simultaneously n=0, m=0 and X¹, X² and X³ are notequal to F, R¹ and R² then do not simultaneously denote H.
 2. A compoundaccording to claim 1, wherein one or more of the radicals X¹, X² and X³denote F.
 3. A compound according to claim 1, wherein X¹ denotes F, Cl,CN or CF₃ and X² and X³ denote hydrogen.
 4. A compound according toclaim 1, wherein X¹ denotes F.
 5. A compound according to claim 1,wherein Z¹ and Z², independently of one another, denote a single bond,—CF₂O—, —OCF₂—, —CF₂CF₂—, —CH═CH—, —CF═CH—, —CH═CF— or —CF═CF—.
 6. Acompound according to claim 1, wherein A¹ and A², independently of oneanother, denote a ring of formula


7. A compound according to claim 1, wherein R¹ and R² each,independently of one another, denote an alkanyl radical, alkoxy radicalor alkenyl radical having up to 7 carbon atoms, where each of theseradicals is unsubstituted or mono- or polysubstituted by halogen, ordenotes fluorine or hydrogen.
 8. A compound according to claim 1,wherein m and n are both zero, and R¹ and R² each, independently of oneanother, are an unbranched alkanyl radical, alkoxy radical or alkenylradical having up to 7 carbon atoms.
 9. A compound according to claim 1,wherein m+n=1, and A¹ and A², independently of one another, denote


10. A compound according to claim 1, wherein m=0, and R¹ is an alkoxyradical or alkenyloxy radical having 2 to 7 carbon atoms.
 11. Aliquid-crystalline media comprising a compound according to claim
 1. 12.A liquid-crystalline medium comprising at least two compounds, whichcomprises at least one compound according to claim
 1. 13. Anelectro-optical display element containing a liquid-crystalline mediumaccording to claim
 12. 14. A process for preparing a compound accordingto claim 1, comprising cyclizing an appropriately substituted2-(2-halophenyl)cyclohexanol compound to give a tetrahydrodibenzofurancompound.